The unique antigen receptor signaling phenotype of B-1 cells is influenced by locale but induced by antigen.
Normal animals contain an autoreactive B lymphocyte subset, the B-1 subset, which is controlled by undefined mechanisms to prevent autoimmunity. Using a V(H)11V(kappa)9 Ig transgenic mouse, with a specificity prototypic of the subset, we have explored conditions responsible for the previously reported Ag hyporesponsiveness of these cells. We report that peritoneal V(H)11V(kappa)9 B cells exhibit typical B-1 behavior with high basal intracellular free Ca(2+) and negligible receptor-mediated calcium mobilization. However, splenic B cells from this mouse, while phenotypically similar to their peritoneal counterparts, including expression of CD5, mount robust B-2-like responses to Ag as measured by calcium influx and altered tyrosine phosphorylation responses. When these splenic cells are adoptively transferred to the peritoneal cavity and encounter their cognate self-Ag, they acquire a B-1 signaling phenotype. The ensuing hyporesponsiveness is characterized by increases in both basal intracellular calcium and resting tyrosyl phosphorylation levels and is highlighted by a marked abrogation of B cell receptor-mediated calcium mobilization. Thus, we show that self-Ag recognition in specific microenvironments such as the peritoneum, and we would propose other privileged sites, confers a unique form of anergy on activated B cells. This may explain how autoreactive B-1 cells can exist while autoimmunity is avoided.
Chumley
Michael J
MJ
Integrated Department of Immunology, National Jewish Medical and Research Center and University of Colorado School of Medicine, Denver, CO 80206, USA.
Dal Porto
Joseph M
JM
Cambier
John C
JC
D019264:Adoptive Transfer; D000818:Animals; D015551:Autoimmunity; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling; D017635:Clonal Anergy; D008213:Lymphocyte Activation; D051379:Mice; D008822:Mice, Transgenic; D018448:Models, Immunological; D010529:Peritoneal Cavity / Q000166:cytology; D010641:Phenotype; D011947:Receptors, Antigen, B-Cell / Q000235:genetics / Q000378:metabolism*; D013154:Spleen / Q000166:cytology / Q000276:immunology
D011947:Receptors, Antigen, B-Cell; D002118:Calcium