Characterization of immature B cells by a novel monoclonal antibody, by turnover and by mitogen reactivity.
The transit of immature to mature sIgM+ B cells, the life span, maturation kinetics and response to polyclonal activators have been analyzed with the help of a new mAb (493), that distinguishes immature, 493+ from mature, 493 B cells in a variety of mouse strains tested. Analysis of the turnover of immature 493+ B cells by bromodeoxyuridine (BrdU) labeling kinetics indicate that only 10-20 % of the cells reach the spleen as immature 493+ cells. The life span of 493+ B cells in bone marrow and spleen is around 4 days. BrdU chase experiments show that most of the immature cells in spleen enter the pool of mature, 493+ B cells where they gain a longer life span of 15-20 weeks. Immature and mature B cells respond equally well to LPS stimulation; anti-CD40, however, stimulates mature B cells better than immature B cells. IgM cross-linking of mature B cells results in proliferation, while it induces apoptosis in immature B cells. This apoptosis of immature cells can be inhibited by costimulation with anti-CD40 or by overexpression of bcl-2. We speculate that Ig receptor ligand-mediated apoptosis (negative selection) plays a major role in the transit of immature B cells from bone marrow to spleen, but only a minor role in the transit from immature B cells to mature B cells in the spleen.
Rolink
A G
AG
Basel Institute for Immunology, Switzerland.
Andersson
J
J
Melchers
F
F
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000276:immunology*; D001402:B-Lymphocytes / Q000502:physiology*; D001973:Bromodeoxyuridine / Q000378:metabolism; D019013:CD40 Antigens / Q000502:physiology; D006412:Hematopoietic Stem Cells / Q000502:physiology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008808:Mice, Inbred CBA; D051381:Rats; D011917:Rats, Inbred Lew
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D019013:CD40 Antigens; D008070:Lipopolysaccharides; C044203:anti-IgM; D001973:Bromodeoxyuridine