B-cell activation by crosslinking of surface IgM or ligation of CD40 involves alternative signal pathways and results in different B-cell phenotypes.
Treatment of small resting B cells with soluble F(ab')2 fragments of anti-IgM, an analogue of T-independent type 2 antigens, induced activation characterized by proliferation and the expression of surface CD5. In contrast, B cells induced to proliferate in response to thymus-dependent inductive signals provided by either fixed activated T-helper 2 cells or soluble CD40 ligand-CD8 (CD40L) recombinant protein displayed elevated levels of CD23 (Fc epsilon II receptor) and no surface CD5. Treatment with anti-IgM and CD40L induced higher levels of proliferation and generated a single population of B cells coexpressing minimal amounts of CD5 and only a slight elevation of CD23. Anti-IgM- but not CD40L-mediated activation was highly sensitive to inhibition by cyclosporin A and FK520. Sp-cAMPS, an analogue of cAMP, augmented CD40L and suppressed surface IgM-mediated activation. Taken together these results are interpreted to mean that there is a single population of small resting B cells that can respond to either T-independent type 2 (surface IgM)- or T-dependent (CD40)-mediated activation. In response to different intracellular signals these cells are induced to enter alternative differentiation pathways.
Wortis
H H
HH
Department of Pathology, Tufts University School of Medicine, Boston, MA 02111, USA.
Teutsch
M
M
Higer
M
M
Zheng
J
J
Parker
D C
DC
D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis / Q000378:metabolism; D000944:Antigens, Differentiation, B-Lymphocyte / Q000378:metabolism; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D019013:CD40 Antigens; D018956:CD5 Antigens; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000494:pharmacology; D016572:Cyclosporine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D007075:Immunoglobulin M / Q000378:metabolism; D007152:Immunologic Capping; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008808:Mice, Inbred CBA; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism; D017455:Receptors, IgE / Q000096:biosynthesis; D015398:Signal Transduction; D013154:Spleen / Q000166:cytology / Q000276:immunology; D016559:Tacrolimus / Q000031:analogs & derivatives / Q000494:pharmacology; D013873:Thionucleotides / Q000494:pharmacology
D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; D019013:CD40 Antigens; D018956:CD5 Antigens; D007075:Immunoglobulin M; D011947:Receptors, Antigen, B-Cell; D017455:Receptors, IgE; D013873:Thionucleotides; C016957:adenosine-3',5'-cyclic phosphorothioate; D016572:Cyclosporine; C058028:immunomycin; D000242:Cyclic AMP; D016559:Tacrolimus