The Regulation of IgA Class Switching

Overview

Journal Nat Rev Immunol

Specialty Allergy & Immunology

Date 2008 May 17

PMID 18483500

Citations 316

Authors

Andrea Cerutti

Affiliations

Soon will be listed here.

Abstract

IgA class switching is the process whereby B cells acquire the expression of IgA, the most abundant antibody isotype in mucosal secretions. IgA class switching occurs via both T-cell-dependent and T-cell-independent pathways, and the antibody targets both pathogenic and commensal microorganisms. This Review describes recent advances indicating that innate immune recognition of microbial signatures at the epithelial-cell barrier is central to the selective induction of mucosal IgA class switching. In addition, the mechanisms of IgA class switching at follicular and extrafollicular sites within the mucosal environment are summarized. A better understanding of these mechanisms may help in the development of more effective mucosal vaccines.

Citing Articles

MAGE-A4 induces non-small cell lung cancer and tumor-promoting plasma cell accumulation.

Armstrong D, Chang C, Hong M, Green L, Shen Y, Hudson W Sci Adv. 2025; 11(7):eads4227.

PMID: 39937892 PMC: 11817953. DOI: 10.1126/sciadv.ads4227.

T Cell Dysregulation in Rheumatoid Arthritis: from Genetic Susceptibility to Established Disease.

Chin A, Small A, Wong S, Wechalekar M Curr Rheumatol Rep. 2025; 27(1):14.

PMID: 39862300 PMC: 11762599. DOI: 10.1007/s11926-025-01180-1.

The LIM-domain-only protein LMO2 and its binding partner LDB1 are differentially required for class switch recombination.

Yang B, Guo Y, Liu L, Huang T, Zhao B, Bai W Proc Natl Acad Sci U S A. 2025; 122(4):e2412376122.

PMID: 39847321 PMC: 11789033. DOI: 10.1073/pnas.2412376122.

Sequential intranasal booster triggers class switching from intramuscularly primed IgG to mucosal IgA against SARS-CoV-2.

Lin Y, Liao X, Cao X, Zhang Z, Wang X, He X J Clin Invest. 2025; 135(5).

PMID: 39808503 PMC: 11870729. DOI: 10.1172/JCI175233.

Role of microRNAs in immunoregulatory functions of epithelial cells.

Jafari N, Abediankenari S BMC Immunol. 2024; 25(1):84.

PMID: 39707170 PMC: 11662810. DOI: 10.1186/s12865-024-00675-3.

References

Fujieda S, Waschek J, Zhang K, Saxon A . Vasoactive intestinal peptide induces S(alpha)/S(mu) switch circular DNA in human B cells. J Clin Invest. 1996; 98(7):1527-32. PMC: 507583. DOI: 10.1172/JCI118944. View

Cerutti A, Zan H, Kim E, Shah S, Schattner E, Schaffer A . Ongoing in vivo immunoglobulin class switch DNA recombination in chronic lymphocytic leukemia B cells. J Immunol. 2002; 169(11):6594-603. PMC: 4625981. DOI: 10.4049/jimmunol.169.11.6594. View

Mond J, Vos Q, Lees A, Snapper C . T cell independent antigens. Curr Opin Immunol. 1995; 7(3):349-54. DOI: 10.1016/0952-7915(95)80109-x. View

Kaminski D, Stavnezer J . Stimuli that enhance IgA class switching increase histone 3 acetylation at S alpha, but poorly stimulate sequential switching from IgG2b. Eur J Immunol. 2006; 37(1):240-51. DOI: 10.1002/eji.200636645. View

Xie X, Pardali E, Holm M, Sideras P, Grundstrom T . AML and Ets proteins regulate the I alpha1 germ-line promoter. Eur J Immunol. 1999; 29(2):488-98. DOI: 10.1002/(SICI)1521-4141(199902)29:02<488::AID-IMMU488>3.0.CO;2-N. View

Favre L, Spertini F, Corthesy B . Secretory IgA possesses intrinsic modulatory properties stimulating mucosal and systemic immune responses. J Immunol. 2005; 175(5):2793-800. DOI: 10.4049/jimmunol.175.5.2793. View

Shi M, Stavnezer J . CBF alpha3 (AML2) is induced by TGF-beta1 to bind and activate the mouse germline Ig alpha promoter. J Immunol. 1998; 161(12):6751-60. View

Hayakawa K, Hardy R . Normal, autoimmune, and malignant CD5+ B cells: the Ly-1 B lineage?. Annu Rev Immunol. 1988; 6:197-218. DOI: 10.1146/annurev.iy.06.040188.001213. View

Snapper C, Zelazowski P, Rosas F, Kehry M, Tian M, Baltimore D . B cells from p50/NF-kappa B knockout mice have selective defects in proliferation, differentiation, germ-line CH transcription, and Ig class switching. J Immunol. 1996; 156(1):183-91. View

10.

Litinskiy M, Nardelli B, Hilbert D, He B, Schaffer A, Casali P . DCs induce CD40-independent immunoglobulin class switching through BLyS and APRIL. Nat Immunol. 2002; 3(9):822-9. PMC: 4621779. DOI: 10.1038/ni829. View

11.

Zhang Y, Derynck R . Transcriptional regulation of the transforming growth factor-beta -inducible mouse germ line Ig alpha constant region gene by functional cooperation of Smad, CREB, and AML family members. J Biol Chem. 2000; 275(22):16979-85. DOI: 10.1074/jbc.M001526200. View

12.

Klein J, Ju W, Heyer J, Wittek B, Haneke T, Knaus P . B cell-specific deficiency for Smad2 in vivo leads to defects in TGF-beta-directed IgA switching and changes in B cell fate. J Immunol. 2006; 176(4):2389-96. DOI: 10.4049/jimmunol.176.4.2389. View

13.

Bollinger R, Everett M, Wahl S, Lee Y, Orndorff P, Parker W . Secretory IgA and mucin-mediated biofilm formation by environmental strains of Escherichia coli: role of type 1 pili. Mol Immunol. 2005; 43(4):378-87. DOI: 10.1016/j.molimm.2005.02.013. View

14.

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

15.

Macpherson A, Harris N . Interactions between commensal intestinal bacteria and the immune system. Nat Rev Immunol. 2004; 4(6):478-85. DOI: 10.1038/nri1373. View

16.

Cunningham-Rundles C, Knight A . Common variable immune deficiency: reviews, continued puzzles, and a new registry. Immunol Res. 2007; 38(1-3):78-86. DOI: 10.1007/s12026-007-0024-0. View

17.

Rodrigo Mora J, Iwata M, Eksteen B, Song S, Junt T, Senman B . Generation of gut-homing IgA-secreting B cells by intestinal dendritic cells. Science. 2006; 314(5802):1157-60. DOI: 10.1126/science.1132742. View

18.

Macpherson A, Uhr T . Induction of protective IgA by intestinal dendritic cells carrying commensal bacteria. Science. 2004; 303(5664):1662-5. DOI: 10.1126/science.1091334. View

19.

Mostov K, Deitcher D . Polymeric immunoglobulin receptor expressed in MDCK cells transcytoses IgA. Cell. 1986; 46(4):613-21. DOI: 10.1016/0092-8674(86)90887-1. View

20.

He B, Qiao X, Cerutti A . CpG DNA induces IgG class switch DNA recombination by activating human B cells through an innate pathway that requires TLR9 and cooperates with IL-10. J Immunol. 2004; 173(7):4479-91. DOI: 10.4049/jimmunol.173.7.4479. View