Peyer's Patches: Organizing B-cell Responses at the Intestinal Frontier

Overview

Journal Immunol Rev

Specialties Allergy & Immunology
General Surgery

Date 2016 Apr 19

PMID 27088918

Citations 137

Authors

Andrea Reboldi

Jason G Cyster

Affiliations

Soon will be listed here.

Abstract

Secondary lymphoid tissues share the important function of bringing together antigens and rare antigen-specific lymphocytes to foster induction of adaptive immune responses. Peyer's patches (PPs) are unique compared to other secondary lymphoid tissues in their continual exposure to an enormous diversity of microbiome- and food-derived antigens and in the types of pathogens they encounter. Antigens are delivered to PPs by specialized microfold (M) epithelial cells and they may be captured and presented by resident dendritic cells (DCs). In accord with their state of chronic microbial antigen exposure, PPs exhibit continual germinal center (GC) activity. These GCs not only contribute to the generation of B cells and plasma cells producing somatically mutated gut antigen-specific IgA antibodies but have also been suggested to support non-specific antigen diversification of the B-cell repertoire. Here, we review current understanding of how PPs foster B-cell encounters with antigen, how they favor isotype switching to the secretory IgA isotype, and how their GC responses may uniquely contribute to mucosal immunity.

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References

Varona R, Villares R, Carramolino L, Goya I, Zaballos A, Gutierrez J . CCR6-deficient mice have impaired leukocyte homeostasis and altered contact hypersensitivity and delayed-type hypersensitivity responses. J Clin Invest. 2001; 107(6):R37-45. PMC: 208945. DOI: 10.1172/JCI11297. View

Macpherson A, Koller Y, McCoy K . The bilateral responsiveness between intestinal microbes and IgA. Trends Immunol. 2015; 36(8):460-70. DOI: 10.1016/j.it.2015.06.006. View

Sugiyama M, Nakato G, Jinnohara T, Akiba H, Okumura K, Ohno H . Expression pattern changes and function of RANKL during mouse lymph node microarchitecture development. Int Immunol. 2012; 24(6):369-78. DOI: 10.1093/intimm/dxs002. View

Cyster J, Schwab S . Sphingosine-1-phosphate and lymphocyte egress from lymphoid organs. Annu Rev Immunol. 2011; 30:69-94. DOI: 10.1146/annurev-immunol-020711-075011. View

Gatto D, Paus D, Basten A, Mackay C, Brink R . Guidance of B cells by the orphan G protein-coupled receptor EBI2 shapes humoral immune responses. Immunity. 2009; 31(2):259-69. DOI: 10.1016/j.immuni.2009.06.016. View

Cazac B, Roes J . TGF-beta receptor controls B cell responsiveness and induction of IgA in vivo. Immunity. 2000; 13(4):443-51. DOI: 10.1016/s1074-7613(00)00044-3. View

Kawamoto S, Tran T, Maruya M, Suzuki K, Doi Y, Tsutsui Y . The inhibitory receptor PD-1 regulates IgA selection and bacterial composition in the gut. Science. 2012; 336(6080):485-9. DOI: 10.1126/science.1217718. View

Bromander A, Ekman L, Kopf M, Nedrud J, Lycke N . IL-6-deficient mice exhibit normal mucosal IgA responses to local immunizations and Helicobacter felis infection. J Immunol. 1996; 156(11):4290-7. View

Bouskra D, Brezillon C, Berard M, Werts C, Varona R, Gomperts Boneca I . Lymphoid tissue genesis induced by commensals through NOD1 regulates intestinal homeostasis. Nature. 2008; 456(7221):507-10. DOI: 10.1038/nature07450. View

10.

Macpherson A, Gatto D, Sainsbury E, Harriman G, Hengartner H, Zinkernagel R . A primitive T cell-independent mechanism of intestinal mucosal IgA responses to commensal bacteria. Science. 2000; 288(5474):2222-6. DOI: 10.1126/science.288.5474.2222. View

11.

Molenaar R, Greuter M, van der Marel A, Roozendaal R, Martin S, Edele F . Lymph node stromal cells support dendritic cell-induced gut-homing of T cells. J Immunol. 2009; 183(10):6395-402. DOI: 10.4049/jimmunol.0900311. View

12.

Shikina T, Hiroi T, Iwatani K, Jang M, Fukuyama S, Tamura M . IgA class switch occurs in the organized nasopharynx- and gut-associated lymphoid tissue, but not in the diffuse lamina propria of airways and gut. J Immunol. 2004; 172(10):6259-64. DOI: 10.4049/jimmunol.172.10.6259. View

13.

van Ginkel F, Wahl S, Kearney J, Kweon M, Fujihashi K, Burrows P . Partial IgA-deficiency with increased Th2-type cytokines in TGF-beta 1 knockout mice. J Immunol. 1999; 163(4):1951-7. View

14.

Macpherson A, Geuking M, Slack E, Hapfelmeier S, McCoy K . The habitat, double life, citizenship, and forgetfulness of IgA. Immunol Rev. 2011; 245(1):132-46. DOI: 10.1111/j.1600-065X.2011.01072.x. View

15.

Seo G, Jang Y, Kim H, Lee M, Park M, Park S . Retinoic acid, acting as a highly specific IgA isotype switch factor, cooperates with TGF-β1 to enhance the overall IgA response. J Leukoc Biol. 2013; 94(2):325-35. DOI: 10.1189/jlb.0313128. View

16.

Casola S, Otipoby K, Alimzhanov M, Humme S, Uyttersprot N, Kutok J . B cell receptor signal strength determines B cell fate. Nat Immunol. 2004; 5(3):317-27. DOI: 10.1038/ni1036. View

17.

MATTIOLI C, TOMASI Jr T . The life span of IgA plasma cells from the mouse intestine. J Exp Med. 1973; 138(2):452-60. PMC: 2139405. DOI: 10.1084/jem.138.2.452. View

18.

Tezuka H, Abe Y, Iwata M, Takeuchi H, Ishikawa H, Matsushita M . Regulation of IgA production by naturally occurring TNF/iNOS-producing dendritic cells. Nature. 2007; 448(7156):929-33. DOI: 10.1038/nature06033. View

19.

Gebert A, Steinmetz I, Fassbender S, Wendlandt K . Antigen transport into Peyer's patches: increased uptake by constant numbers of M cells. Am J Pathol. 2003; 164(1):65-72. PMC: 1602236. DOI: 10.1016/S0002-9440(10)63097-0. View

20.

Zhai S, Lanning D . Diversification of the primary antibody repertoire begins during early follicle development in the rabbit appendix. Mol Immunol. 2012; 54(2):140-7. DOI: 10.1016/j.molimm.2012.11.010. View