The role of Peyer´s patches in synchronizing gut IgA responses

Because Peyer’s patches (PP) are the main inductive sites for gut IgA responses we have focused this review on what we know about the function of PP germinal center (GC). The vast majority of IgA gene sequences in the gut lamina propria (LP) are heavily mutated arguing for an origin in GC. Because PP GC formation is dependent on the presence of CD4 T cells, we speculate that all IgA responses in the normal gut are directly or indirectly T cell-dependent. We hypothesize that the CD4 T cell involvement in gut IgA responses against the microbiota is different from that in systemic responses since cognate T-B cell interactions appear not to be required. In the absence of cognate interactions the function of CD4 follicular helper T cells (Tfh) in PP GC is unclear. However, production of IL-21 and IL-6 is more pronounced than in peripheral lymph nodes. Importantly, we discuss how multiple PP are involved in generating specific IgA responses to T cell-dependent (TD) antigens given orally. Recently we found that oral immunization with NP-hapten conjugated to cholera toxin (NP-CT) stimulated a strong highly synchronized, oligoclonal and affinity matured IgA response. This was achieved through re-utilization of GC in multiple PP as GC IgA B cells emigrated into already established GC. Clonally related B cells were present in both inductive and effector lymphoid tissues in the gut and clonal trees involving multiple PP could be constructed in individual mice. Through adoptive transfer of B1-8hi NP-specific B cells we demonstrated that GL7+ PP B cells could enter into pre-existing GC in PP, a process that was antigen-dependent but did not to require cognate Tfh interactions. Finally, we discuss the role of PP GC for the generation of memory B cells and long-lived plasma cells in the light of contrasting findings regarding IgA memory development to colonizing commensal bacteria versus oral immunization with enteropathogens or TD antigens. Ausführliche Beschreibung

Gespeichert in:

Autor*in:	Nils Yngve Lycke [verfasserIn] Mats eBemark [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2012

Schlagwörter:	Cholera Toxin gut IgA Peyer’s patches B cells and germinal centers germinal center re-utilization

Übergeordnetes Werk:	In: Frontiers in Immunology - Frontiers Media S.A., 2011, 3(2012)
Übergeordnetes Werk:	volume:3 ; year:2012

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.3389/fimmu.2012.00329

Katalog-ID:	DOAJ002494779

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allfields	10.3389/fimmu.2012.00329 doi (DE-627)DOAJ002494779 (DE-599)DOAJ9363e904c1754df19d965f37911e87be DE-627 ger DE-627 rakwb eng RC581-607 Nils Yngve Lycke verfasserin aut The role of Peyer´s patches in synchronizing gut IgA responses 2012 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Because Peyer’s patches (PP) are the main inductive sites for gut IgA responses we have focused this review on what we know about the function of PP germinal center (GC). The vast majority of IgA gene sequences in the gut lamina propria (LP) are heavily mutated arguing for an origin in GC. Because PP GC formation is dependent on the presence of CD4 T cells, we speculate that all IgA responses in the normal gut are directly or indirectly T cell-dependent. We hypothesize that the CD4 T cell involvement in gut IgA responses against the microbiota is different from that in systemic responses since cognate T-B cell interactions appear not to be required. In the absence of cognate interactions the function of CD4 follicular helper T cells (Tfh) in PP GC is unclear. However, production of IL-21 and IL-6 is more pronounced than in peripheral lymph nodes. Importantly, we discuss how multiple PP are involved in generating specific IgA responses to T cell-dependent (TD) antigens given orally. Recently we found that oral immunization with NP-hapten conjugated to cholera toxin (NP-CT) stimulated a strong highly synchronized, oligoclonal and affinity matured IgA response. This was achieved through re-utilization of GC in multiple PP as GC IgA B cells emigrated into already established GC. Clonally related B cells were present in both inductive and effector lymphoid tissues in the gut and clonal trees involving multiple PP could be constructed in individual mice. Through adoptive transfer of B1-8hi NP-specific B cells we demonstrated that GL7+ PP B cells could enter into pre-existing GC in PP, a process that was antigen-dependent but did not to require cognate Tfh interactions. Finally, we discuss the role of PP GC for the generation of memory B cells and long-lived plasma cells in the light of contrasting findings regarding IgA memory development to colonizing commensal bacteria versus oral immunization with enteropathogens or TD antigens. Cholera Toxin gut IgA Peyer’s patches B cells and germinal centers germinal center re-utilization Immunologic diseases. Allergy Mats eBemark verfasserin aut In Frontiers in Immunology Frontiers Media S.A., 2011 3(2012) (DE-627)657998354 (DE-600)2606827-8 16643224 nnns volume:3 year:2012 https://doi.org/10.3389/fimmu.2012.00329 kostenfrei https://doaj.org/article/9363e904c1754df19d965f37911e87be kostenfrei http://journal.frontiersin.org/Journal/10.3389/fimmu.2012.00329/full kostenfrei https://doaj.org/toc/1664-3224 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 3 2012
spelling	10.3389/fimmu.2012.00329 doi (DE-627)DOAJ002494779 (DE-599)DOAJ9363e904c1754df19d965f37911e87be DE-627 ger DE-627 rakwb eng RC581-607 Nils Yngve Lycke verfasserin aut The role of Peyer´s patches in synchronizing gut IgA responses 2012 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Because Peyer’s patches (PP) are the main inductive sites for gut IgA responses we have focused this review on what we know about the function of PP germinal center (GC). The vast majority of IgA gene sequences in the gut lamina propria (LP) are heavily mutated arguing for an origin in GC. Because PP GC formation is dependent on the presence of CD4 T cells, we speculate that all IgA responses in the normal gut are directly or indirectly T cell-dependent. We hypothesize that the CD4 T cell involvement in gut IgA responses against the microbiota is different from that in systemic responses since cognate T-B cell interactions appear not to be required. In the absence of cognate interactions the function of CD4 follicular helper T cells (Tfh) in PP GC is unclear. However, production of IL-21 and IL-6 is more pronounced than in peripheral lymph nodes. Importantly, we discuss how multiple PP are involved in generating specific IgA responses to T cell-dependent (TD) antigens given orally. Recently we found that oral immunization with NP-hapten conjugated to cholera toxin (NP-CT) stimulated a strong highly synchronized, oligoclonal and affinity matured IgA response. This was achieved through re-utilization of GC in multiple PP as GC IgA B cells emigrated into already established GC. Clonally related B cells were present in both inductive and effector lymphoid tissues in the gut and clonal trees involving multiple PP could be constructed in individual mice. Through adoptive transfer of B1-8hi NP-specific B cells we demonstrated that GL7+ PP B cells could enter into pre-existing GC in PP, a process that was antigen-dependent but did not to require cognate Tfh interactions. Finally, we discuss the role of PP GC for the generation of memory B cells and long-lived plasma cells in the light of contrasting findings regarding IgA memory development to colonizing commensal bacteria versus oral immunization with enteropathogens or TD antigens. Cholera Toxin gut IgA Peyer’s patches B cells and germinal centers germinal center re-utilization Immunologic diseases. Allergy Mats eBemark verfasserin aut In Frontiers in Immunology Frontiers Media S.A., 2011 3(2012) (DE-627)657998354 (DE-600)2606827-8 16643224 nnns volume:3 year:2012 https://doi.org/10.3389/fimmu.2012.00329 kostenfrei https://doaj.org/article/9363e904c1754df19d965f37911e87be kostenfrei http://journal.frontiersin.org/Journal/10.3389/fimmu.2012.00329/full kostenfrei https://doaj.org/toc/1664-3224 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 3 2012
allfields_unstemmed	10.3389/fimmu.2012.00329 doi (DE-627)DOAJ002494779 (DE-599)DOAJ9363e904c1754df19d965f37911e87be DE-627 ger DE-627 rakwb eng RC581-607 Nils Yngve Lycke verfasserin aut The role of Peyer´s patches in synchronizing gut IgA responses 2012 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Because Peyer’s patches (PP) are the main inductive sites for gut IgA responses we have focused this review on what we know about the function of PP germinal center (GC). The vast majority of IgA gene sequences in the gut lamina propria (LP) are heavily mutated arguing for an origin in GC. Because PP GC formation is dependent on the presence of CD4 T cells, we speculate that all IgA responses in the normal gut are directly or indirectly T cell-dependent. We hypothesize that the CD4 T cell involvement in gut IgA responses against the microbiota is different from that in systemic responses since cognate T-B cell interactions appear not to be required. In the absence of cognate interactions the function of CD4 follicular helper T cells (Tfh) in PP GC is unclear. However, production of IL-21 and IL-6 is more pronounced than in peripheral lymph nodes. Importantly, we discuss how multiple PP are involved in generating specific IgA responses to T cell-dependent (TD) antigens given orally. Recently we found that oral immunization with NP-hapten conjugated to cholera toxin (NP-CT) stimulated a strong highly synchronized, oligoclonal and affinity matured IgA response. This was achieved through re-utilization of GC in multiple PP as GC IgA B cells emigrated into already established GC. Clonally related B cells were present in both inductive and effector lymphoid tissues in the gut and clonal trees involving multiple PP could be constructed in individual mice. Through adoptive transfer of B1-8hi NP-specific B cells we demonstrated that GL7+ PP B cells could enter into pre-existing GC in PP, a process that was antigen-dependent but did not to require cognate Tfh interactions. Finally, we discuss the role of PP GC for the generation of memory B cells and long-lived plasma cells in the light of contrasting findings regarding IgA memory development to colonizing commensal bacteria versus oral immunization with enteropathogens or TD antigens. Cholera Toxin gut IgA Peyer’s patches B cells and germinal centers germinal center re-utilization Immunologic diseases. Allergy Mats eBemark verfasserin aut In Frontiers in Immunology Frontiers Media S.A., 2011 3(2012) (DE-627)657998354 (DE-600)2606827-8 16643224 nnns volume:3 year:2012 https://doi.org/10.3389/fimmu.2012.00329 kostenfrei https://doaj.org/article/9363e904c1754df19d965f37911e87be kostenfrei http://journal.frontiersin.org/Journal/10.3389/fimmu.2012.00329/full kostenfrei https://doaj.org/toc/1664-3224 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 3 2012
allfieldsGer	10.3389/fimmu.2012.00329 doi (DE-627)DOAJ002494779 (DE-599)DOAJ9363e904c1754df19d965f37911e87be DE-627 ger DE-627 rakwb eng RC581-607 Nils Yngve Lycke verfasserin aut The role of Peyer´s patches in synchronizing gut IgA responses 2012 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Because Peyer’s patches (PP) are the main inductive sites for gut IgA responses we have focused this review on what we know about the function of PP germinal center (GC). The vast majority of IgA gene sequences in the gut lamina propria (LP) are heavily mutated arguing for an origin in GC. Because PP GC formation is dependent on the presence of CD4 T cells, we speculate that all IgA responses in the normal gut are directly or indirectly T cell-dependent. We hypothesize that the CD4 T cell involvement in gut IgA responses against the microbiota is different from that in systemic responses since cognate T-B cell interactions appear not to be required. In the absence of cognate interactions the function of CD4 follicular helper T cells (Tfh) in PP GC is unclear. However, production of IL-21 and IL-6 is more pronounced than in peripheral lymph nodes. Importantly, we discuss how multiple PP are involved in generating specific IgA responses to T cell-dependent (TD) antigens given orally. Recently we found that oral immunization with NP-hapten conjugated to cholera toxin (NP-CT) stimulated a strong highly synchronized, oligoclonal and affinity matured IgA response. This was achieved through re-utilization of GC in multiple PP as GC IgA B cells emigrated into already established GC. Clonally related B cells were present in both inductive and effector lymphoid tissues in the gut and clonal trees involving multiple PP could be constructed in individual mice. Through adoptive transfer of B1-8hi NP-specific B cells we demonstrated that GL7+ PP B cells could enter into pre-existing GC in PP, a process that was antigen-dependent but did not to require cognate Tfh interactions. Finally, we discuss the role of PP GC for the generation of memory B cells and long-lived plasma cells in the light of contrasting findings regarding IgA memory development to colonizing commensal bacteria versus oral immunization with enteropathogens or TD antigens. Cholera Toxin gut IgA Peyer’s patches B cells and germinal centers germinal center re-utilization Immunologic diseases. Allergy Mats eBemark verfasserin aut In Frontiers in Immunology Frontiers Media S.A., 2011 3(2012) (DE-627)657998354 (DE-600)2606827-8 16643224 nnns volume:3 year:2012 https://doi.org/10.3389/fimmu.2012.00329 kostenfrei https://doaj.org/article/9363e904c1754df19d965f37911e87be kostenfrei http://journal.frontiersin.org/Journal/10.3389/fimmu.2012.00329/full kostenfrei https://doaj.org/toc/1664-3224 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 3 2012
allfieldsSound	10.3389/fimmu.2012.00329 doi (DE-627)DOAJ002494779 (DE-599)DOAJ9363e904c1754df19d965f37911e87be DE-627 ger DE-627 rakwb eng RC581-607 Nils Yngve Lycke verfasserin aut The role of Peyer´s patches in synchronizing gut IgA responses 2012 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Because Peyer’s patches (PP) are the main inductive sites for gut IgA responses we have focused this review on what we know about the function of PP germinal center (GC). The vast majority of IgA gene sequences in the gut lamina propria (LP) are heavily mutated arguing for an origin in GC. Because PP GC formation is dependent on the presence of CD4 T cells, we speculate that all IgA responses in the normal gut are directly or indirectly T cell-dependent. We hypothesize that the CD4 T cell involvement in gut IgA responses against the microbiota is different from that in systemic responses since cognate T-B cell interactions appear not to be required. In the absence of cognate interactions the function of CD4 follicular helper T cells (Tfh) in PP GC is unclear. However, production of IL-21 and IL-6 is more pronounced than in peripheral lymph nodes. Importantly, we discuss how multiple PP are involved in generating specific IgA responses to T cell-dependent (TD) antigens given orally. Recently we found that oral immunization with NP-hapten conjugated to cholera toxin (NP-CT) stimulated a strong highly synchronized, oligoclonal and affinity matured IgA response. This was achieved through re-utilization of GC in multiple PP as GC IgA B cells emigrated into already established GC. Clonally related B cells were present in both inductive and effector lymphoid tissues in the gut and clonal trees involving multiple PP could be constructed in individual mice. Through adoptive transfer of B1-8hi NP-specific B cells we demonstrated that GL7+ PP B cells could enter into pre-existing GC in PP, a process that was antigen-dependent but did not to require cognate Tfh interactions. Finally, we discuss the role of PP GC for the generation of memory B cells and long-lived plasma cells in the light of contrasting findings regarding IgA memory development to colonizing commensal bacteria versus oral immunization with enteropathogens or TD antigens. Cholera Toxin gut IgA Peyer’s patches B cells and germinal centers germinal center re-utilization Immunologic diseases. Allergy Mats eBemark verfasserin aut In Frontiers in Immunology Frontiers Media S.A., 2011 3(2012) (DE-627)657998354 (DE-600)2606827-8 16643224 nnns volume:3 year:2012 https://doi.org/10.3389/fimmu.2012.00329 kostenfrei https://doaj.org/article/9363e904c1754df19d965f37911e87be kostenfrei http://journal.frontiersin.org/Journal/10.3389/fimmu.2012.00329/full kostenfrei https://doaj.org/toc/1664-3224 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 3 2012
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callnumber-first	R - Medicine
author	Nils Yngve Lycke
spellingShingle	Nils Yngve Lycke misc RC581-607 misc Cholera Toxin misc gut IgA misc Peyer’s patches misc B cells and germinal centers misc germinal center re-utilization misc Immunologic diseases. Allergy The role of Peyer´s patches in synchronizing gut IgA responses
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topic_title	RC581-607 The role of Peyer´s patches in synchronizing gut IgA responses Cholera Toxin gut IgA Peyer’s patches B cells and germinal centers germinal center re-utilization
topic	misc RC581-607 misc Cholera Toxin misc gut IgA misc Peyer’s patches misc B cells and germinal centers misc germinal center re-utilization misc Immunologic diseases. Allergy
topic_unstemmed	misc RC581-607 misc Cholera Toxin misc gut IgA misc Peyer’s patches misc B cells and germinal centers misc germinal center re-utilization misc Immunologic diseases. Allergy
topic_browse	misc RC581-607 misc Cholera Toxin misc gut IgA misc Peyer’s patches misc B cells and germinal centers misc germinal center re-utilization misc Immunologic diseases. Allergy
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title	The role of Peyer´s patches in synchronizing gut IgA responses
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title_full	The role of Peyer´s patches in synchronizing gut IgA responses
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title_sort	role of peyer´s patches in synchronizing gut iga responses
callnumber	RC581-607
title_auth	The role of Peyer´s patches in synchronizing gut IgA responses
abstract	Because Peyer’s patches (PP) are the main inductive sites for gut IgA responses we have focused this review on what we know about the function of PP germinal center (GC). The vast majority of IgA gene sequences in the gut lamina propria (LP) are heavily mutated arguing for an origin in GC. Because PP GC formation is dependent on the presence of CD4 T cells, we speculate that all IgA responses in the normal gut are directly or indirectly T cell-dependent. We hypothesize that the CD4 T cell involvement in gut IgA responses against the microbiota is different from that in systemic responses since cognate T-B cell interactions appear not to be required. In the absence of cognate interactions the function of CD4 follicular helper T cells (Tfh) in PP GC is unclear. However, production of IL-21 and IL-6 is more pronounced than in peripheral lymph nodes. Importantly, we discuss how multiple PP are involved in generating specific IgA responses to T cell-dependent (TD) antigens given orally. Recently we found that oral immunization with NP-hapten conjugated to cholera toxin (NP-CT) stimulated a strong highly synchronized, oligoclonal and affinity matured IgA response. This was achieved through re-utilization of GC in multiple PP as GC IgA B cells emigrated into already established GC. Clonally related B cells were present in both inductive and effector lymphoid tissues in the gut and clonal trees involving multiple PP could be constructed in individual mice. Through adoptive transfer of B1-8hi NP-specific B cells we demonstrated that GL7+ PP B cells could enter into pre-existing GC in PP, a process that was antigen-dependent but did not to require cognate Tfh interactions. Finally, we discuss the role of PP GC for the generation of memory B cells and long-lived plasma cells in the light of contrasting findings regarding IgA memory development to colonizing commensal bacteria versus oral immunization with enteropathogens or TD antigens.
abstractGer	Because Peyer’s patches (PP) are the main inductive sites for gut IgA responses we have focused this review on what we know about the function of PP germinal center (GC). The vast majority of IgA gene sequences in the gut lamina propria (LP) are heavily mutated arguing for an origin in GC. Because PP GC formation is dependent on the presence of CD4 T cells, we speculate that all IgA responses in the normal gut are directly or indirectly T cell-dependent. We hypothesize that the CD4 T cell involvement in gut IgA responses against the microbiota is different from that in systemic responses since cognate T-B cell interactions appear not to be required. In the absence of cognate interactions the function of CD4 follicular helper T cells (Tfh) in PP GC is unclear. However, production of IL-21 and IL-6 is more pronounced than in peripheral lymph nodes. Importantly, we discuss how multiple PP are involved in generating specific IgA responses to T cell-dependent (TD) antigens given orally. Recently we found that oral immunization with NP-hapten conjugated to cholera toxin (NP-CT) stimulated a strong highly synchronized, oligoclonal and affinity matured IgA response. This was achieved through re-utilization of GC in multiple PP as GC IgA B cells emigrated into already established GC. Clonally related B cells were present in both inductive and effector lymphoid tissues in the gut and clonal trees involving multiple PP could be constructed in individual mice. Through adoptive transfer of B1-8hi NP-specific B cells we demonstrated that GL7+ PP B cells could enter into pre-existing GC in PP, a process that was antigen-dependent but did not to require cognate Tfh interactions. Finally, we discuss the role of PP GC for the generation of memory B cells and long-lived plasma cells in the light of contrasting findings regarding IgA memory development to colonizing commensal bacteria versus oral immunization with enteropathogens or TD antigens.
abstract_unstemmed	Because Peyer’s patches (PP) are the main inductive sites for gut IgA responses we have focused this review on what we know about the function of PP germinal center (GC). The vast majority of IgA gene sequences in the gut lamina propria (LP) are heavily mutated arguing for an origin in GC. Because PP GC formation is dependent on the presence of CD4 T cells, we speculate that all IgA responses in the normal gut are directly or indirectly T cell-dependent. We hypothesize that the CD4 T cell involvement in gut IgA responses against the microbiota is different from that in systemic responses since cognate T-B cell interactions appear not to be required. In the absence of cognate interactions the function of CD4 follicular helper T cells (Tfh) in PP GC is unclear. However, production of IL-21 and IL-6 is more pronounced than in peripheral lymph nodes. Importantly, we discuss how multiple PP are involved in generating specific IgA responses to T cell-dependent (TD) antigens given orally. Recently we found that oral immunization with NP-hapten conjugated to cholera toxin (NP-CT) stimulated a strong highly synchronized, oligoclonal and affinity matured IgA response. This was achieved through re-utilization of GC in multiple PP as GC IgA B cells emigrated into already established GC. Clonally related B cells were present in both inductive and effector lymphoid tissues in the gut and clonal trees involving multiple PP could be constructed in individual mice. Through adoptive transfer of B1-8hi NP-specific B cells we demonstrated that GL7+ PP B cells could enter into pre-existing GC in PP, a process that was antigen-dependent but did not to require cognate Tfh interactions. Finally, we discuss the role of PP GC for the generation of memory B cells and long-lived plasma cells in the light of contrasting findings regarding IgA memory development to colonizing commensal bacteria versus oral immunization with enteropathogens or TD antigens.
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title_short	The role of Peyer´s patches in synchronizing gut IgA responses
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The role of Peyer´s patches in synchronizing gut IgA responses

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