title: Secreted IgM enhances B cell receptor signaling and promotes splenic but impairs peritoneal B cell survival.
abstract: B cell survival has a central role in maintaining immune responses to foreign organisms while curbing autoimmunity. In this study, we show that mature B cell survival is impaired and B cell turnover is accelerated in the spleen of mice lacking secreted IgM. Although in vitro responses to BCR cross-linking were normal, there was a marked reduction in basal ERK and global tyrosine phosphorylation in splenic B cells from serum IgM-deficient mice, suggesting diminished interaction with cognate Ag in vivo. The provision of BAFF either in vitro or in vivo reversed the increase in B cell apoptosis, demonstrating that other survival signals can compensate for the loss of secreted IgM in the spleen. In striking contrast to the splenic compartment, peritoneal B cell survival was enhanced in secreted IgM-deficient mice, despite a similar reduction in basal BCR signaling compared with wild type mice. These results suggest that secreted IgM acts as an adjuvant, boosting BCR signals to maintain survival and maintenance of mature splenic B cells while increasing B cell apoptosis in the peritoneum. BAFF administration mitigated the consequences of secreted IgM deficiency on B cell survival in the spleen but not in the peritoneum. This work provides new insight into the regulation of B cell signaling and homeostasis in different peripheral compartments by secreted IgM.
authors.affiliation: Division of Medicine, Centre for Rheumatology, University College London, London, United Kingdom.
authors.forename: Clare A
authors.initials: CA
authors.lastname: Notley
authors.forename: Nicole
authors.initials: N
authors.lastname: Baker
authors.forename: Michael R
authors.initials: MR
authors.lastname: Ehrenstein
mesh_terms: D000818:Animals; D053264:B-Cell Activating Factor; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002469:Cell Separation; D002470:Cell Survival; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D015151:Immunoblotting; D007075:Immunoglobulin M / Q000172:deficiency / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D010537:Peritoneum / Q000166:cytology / Q000276:immunology*; D011947:Receptors, Antigen, B-Cell / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology*; D013154:Spleen / Q000166:cytology / Q000276:immunology*
chemical_list: D053264:B-Cell Activating Factor; D007075:Immunoglobulin M; D011947:Receptors, Antigen, B-Cell; C505720:Tnfsf13b protein, mouse