Secreted IgM Modulates IL-10 Expression in B Cells

Overview

Journal Nat Commun

Specialty Biology

Date 2024 Jan 5

PMID 38182585

Authors

Shannon Eileen McGettigan

Lazaro Emilio Aira

Gaurav Kumar

Romain Ballet

Eugene C Butcher

Nicole Baumgarth

Gudrun F Debes

Affiliations

Soon will be listed here.

Abstract

IL-10 B cells are critical for immune homeostasis and restraining immune responses in infection, cancer, and inflammation; however, the signals that govern IL-10 B cell differentiation are ill-defined. Here we find that IL-10 B cells expand in mice lacking secreted IgM ((s)IgM) up to 10-fold relative to wildtype (WT) among all major B cell and regulatory B cell subsets. The IL-10 B cell increase is polyclonal and presents within 24 hours of birth. In WT mice, sIgM is produced prenatally and limits the expansion of IL-10 B cells. Lack of the high affinity receptor for sIgM, FcμR, in B cells translates into an intermediate IL-10 B cell phenotype relative to WT or sIgM mice. Our study thus shows that sIgM regulates IL-10 programming in B cells in part via B cell-expressed FcμR, thereby revealing a function of sIgM in regulating immune homeostasis.

References

Kollmann T, Kampmann B, Mazmanian S, Marchant A, Levy O . Protecting the Newborn and Young Infant from Infectious Diseases: Lessons from Immune Ontogeny. Immunity. 2017; 46(3):350-363. DOI: 10.1016/j.immuni.2017.03.009. View

Sutton B . Multi-faceted immunoglobulin M meets its elusive receptor. Nat Struct Mol Biol. 2023; 30(7):866-869. DOI: 10.1038/s41594-023-01030-7. View

Cerutti A, Cols M, Puga I . Marginal zone B cells: virtues of innate-like antibody-producing lymphocytes. Nat Rev Immunol. 2013; 13(2):118-32. PMC: 3652659. DOI: 10.1038/nri3383. View

Louis A, Agrawal S, Gupta S . Analysis of subsets of B cells, Breg, CD4Treg and CD8Treg cells in adult patients with primary selective IgM deficiency. Am J Clin Exp Immunol. 2016; 5(1):21-32. PMC: 4858603. View

Iovino F, Molema G, Bijlsma J . Streptococcus pneumoniae Interacts with pIgR expressed by the brain microvascular endothelium but does not co-localize with PAF receptor. PLoS One. 2014; 9(5):e97914. PMC: 4026408. DOI: 10.1371/journal.pone.0097914. View

Kubagawa H, Skopnik C, Zimmermann J, Durek P, Chang H, Yoo E . Authentic IgM Fc Receptor (FcμR). Curr Top Microbiol Immunol. 2017; 408:25-45. DOI: 10.1007/82_2017_23. View

Shinde R, McGaha T . The Aryl Hydrocarbon Receptor: Connecting Immunity to the Microenvironment. Trends Immunol. 2018; 39(12):1005-1020. PMC: 7182078. DOI: 10.1016/j.it.2018.10.010. View

Walker W, Goldstein D . Neonatal B cells suppress innate toll-like receptor immune responses and modulate alloimmunity. J Immunol. 2007; 179(3):1700-10. DOI: 10.4049/jimmunol.179.3.1700. View

Yu J, Duong V, Westphal K, Westphal A, Suwandi A, Grassl G . Surface receptor Toso controls B cell-mediated regulation of T cell immunity. J Clin Invest. 2018; 128(5):1820-1836. PMC: 5919877. DOI: 10.1172/JCI97280. View

10.

Collins A, Watson C . Immunoglobulin Light Chain Gene Rearrangements, Receptor Editing and the Development of a Self-Tolerant Antibody Repertoire. Front Immunol. 2018; 9:2249. PMC: 6186787. DOI: 10.3389/fimmu.2018.02249. View

11.

Baumgarth N . The double life of a B-1 cell: self-reactivity selects for protective effector functions. Nat Rev Immunol. 2010; 11(1):34-46. DOI: 10.1038/nri2901. View

12.

Van Furth R, SCHUIT H, HIJMANS W . The immunological development of the human fetus. J Exp Med. 1965; 122(6):1173-88. PMC: 2138097. DOI: 10.1084/jem.122.6.1173. View

13.

Adachi T, Harumiya S, Takematsu H, Kozutsumi Y, Wabl M, Fujimoto M . CD22 serves as a receptor for soluble IgM. Eur J Immunol. 2011; 42(1):241-7. DOI: 10.1002/eji.201141899. View

14.

Blandino R, Baumgarth N . Secreted IgM: New tricks for an old molecule. J Leukoc Biol. 2019; 106(5):1021-1034. PMC: 6803036. DOI: 10.1002/JLB.3RI0519-161R. View

15.

Jackson-Jones L, Duncan S, Magalhaes M, Campbell S, Maizels R, McSorley H . Fat-associated lymphoid clusters control local IgM secretion during pleural infection and lung inflammation. Nat Commun. 2016; 7:12651. PMC: 5025788. DOI: 10.1038/ncomms12651. View

16.

Smith F, Savage H, Luo Z, Tipton C, Lee F, Apostol A . B-1 plasma cells require non-cognate CD4 T cell help to generate a unique repertoire of natural IgM. J Exp Med. 2023; 220(4). PMC: 9960156. DOI: 10.1084/jem.20220195. View

17.

Maseda D, Smith S, DiLillo D, Bryant J, Candando K, Weaver C . Regulatory B10 cells differentiate into antibody-secreting cells after transient IL-10 production in vivo. J Immunol. 2011; 188(3):1036-48. PMC: 3262922. DOI: 10.4049/jimmunol.1102500. View

18.

Liu J, Wang Y, Xiong E, Hong R, Lu Q, Ohno H . Role of the IgM Fc Receptor in Immunity and Tolerance. Front Immunol. 2019; 10:529. PMC: 6438924. DOI: 10.3389/fimmu.2019.00529. View

19.

Gleeson J, Fein K, Chaudhary N, Doerfler R, Newby A, Whitehead K . The enhanced intestinal permeability of infant mice enables oral protein and macromolecular absorption without delivery technology. Int J Pharm. 2020; 593:120120. PMC: 7790917. DOI: 10.1016/j.ijpharm.2020.120120. View

20.

Kalampokis I, Venturi G, Poe J, Dvergsten J, Sleasman J, Tedder T . The Regulatory B Cell Compartment Expands Transiently During Childhood and Is Contracted in Children With Autoimmunity. Arthritis Rheumatol. 2016; 69(1):225-238. PMC: 5195882. DOI: 10.1002/art.39820. View