Evidence for selection of a population of multi-reactive B cells into the splenic marginal zone.
Antibody reactivity to self-antigens is a normal component of the immune system. To study the mechanism by which self-reactive B cells are generated and maintained, we analyzed B cell development in transgenic mice that express a rearranged VH81X heavy chain from the pre-immune repertoire. In these mice, > 95% of B cells express the transgene in association with a variety of kappa light chains but V kappa 1 C being the dominant light chain. These transgenic B cells with identical V kappa 1C-J kappa 5 joins do not normally secrete IgM in vivo, but antibodies derived from these B cells, through LPS activation in vitro or after hybridoma immortalization, are self-reactive and recognize an ubiquitous epitope(s) on intracytoplasmic proteins from different tissues. They have the phenotype and localization pattern of long-lived marginal zone B cells and their development in vivo is blocked by injection of soluble VH81X-V kappa 1CJ kappa 5 IgM antibody. The observations in this transgenic mouse provide evidence for positive selection of a population of self-reactive B cells. These B cells enter the peripheral pool of B cells where they localize in the marginal zone of the spleen and, in contrast to other transgene-expressing B cells, do not secrete IgM antibody.
Chen
X
X
Department of Microbiology, University of Alabama at Birmingham 35294-3300, USA.
Martin
F
F
Forbush
K A
KA
Perlmutter
R M
RM
Kearney
J F
JF
D000818:Animals; D000906:Antibodies / Q000097:blood; D001324:Autoantigens / Q000276:immunology; D016175:B-Lymphocyte Subsets / Q000145:classification / Q000276:immunology* / Q000378:metabolism; D015322:Gene Rearrangement, B-Lymphocyte / Q000276:immunology; D006207:Half-Life; D007143:Immunoglobulin Heavy Chains / Q000097:blood; D007130:Immunoglobulin Idiotypes / Q000008:administration & dosage / Q000096:biosynthesis / Q000378:metabolism; D007135:Immunoglobulin Variable Region / Q000235:genetics; D007145:Immunoglobulin kappa-Chains / Q000235:genetics; D016130:Immunophenotyping; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D013154:Spleen / Q000166:cytology* / Q000276:immunology*
D000906:Antibodies; D001324:Autoantigens; D007143:Immunoglobulin Heavy Chains; D007130:Immunoglobulin Idiotypes; D007135:Immunoglobulin Variable Region; D007145:Immunoglobulin kappa-Chains