Antigen-induced exclusion from follicles and anergy are separate and complementary processes that influence peripheral B cell fate.
Anergic self-reactive B cells competing within a polyclonal B cell repertoire fail to migrate into primary follicles and die after 1-3 days residence in T cell zones. Transfer of anergic HEL-specific B cells to recipients lacking HEL autoantigen and continuous bromodeoxyuridine labeling in mixed bone marrow chimeras confirms that follicular exclusion and cell death in 1-3 days is not an intrinsic characteristic of anergic cells but results from competition with B cells bearing other specificities together with continued binding of autoantigen. When naive (nontolerant) HEL-specific B cells were transferred into mice expressing HEL autoantigen, they were also excluded from follicles and their lifespan was dramatically shortened, although they became activated to express CD86 (B7-2/B70). In the presence of helper T cells, activated B cells but not anergic B cells were rescued from death and formed large extrafollicular foci to autoantibody-secreting cells. Antigen-induced exclusion from follicles is therefore an independent process from anergy that prevents self-reactive B cells from recirculating in the long-lived repertoire and may foster interactions with T cells during immune responses. By contrast, anergy prevents self-reactive B cells from collaborating with helper T cells and secreting autoantibody while trapped in the T zone.
Cyster
J G
JG
Department of Microbiology and Immunology, Stanford University School of Medicine, California 94305, USA.
Goodnow
C C
CC
D000818:Animals; D000906:Antibodies / Q000276:immunology; D001324:Autoantigens / Q000276:immunology*; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D016923:Cell Death; D002465:Cell Movement; D017635:Clonal Anergy; D008213:Lymphocyte Activation; D008211:Lymphocyte Cooperation; D008221:Lymphoid Tissue / Q000166:cytology / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D009113:Muramidase / Q000276:immunology
D000906:Antibodies; D001324:Autoantigens; D009113:Muramidase