B-Cell Activation by Crosslinking of Surface IgM or Ligation of CD40 Involves Alternative Signal Pathways and Results in Different B-Cell Phenotypes

• Published in: Proceedings of the National Academy of Sciences - PNAS 1995-04, Vol.92 (8), p.3348-3352
• Main Authors: Wortis, Henry H., Teutsch, Mark, Higer, Mindy, Zheng, Jenny, Parker, David C.
• Format: Article
• Language: English
• Subjects: Animals; Antibodies; Antigens; Antigens, CD - biosynthesis; Antigens, CD - metabolism; Antigens, Differentiation, B-Lymphocyte - metabolism; B lymphocytes; B-Lymphocytes - drug effects; B-Lymphocytes - immunology; Biochemistry; CD40 Antigens; CD5 Antigens; Cells, Cultured; Cellular biology; Crosslinking; Cultured cells; Cyclic AMP - analogs & derivatives; Cyclic AMP - pharmacology; Cyclosporine - pharmacology; Cytometry; Dose-Response Relationship, Drug; Flow Cytometry; Immunoglobulin M - metabolism; Immunologic Capping; Immunology; Ligation; Lymphocyte Activation - immunology; Mice; Mice, Inbred BALB C; Mice, Inbred CBA; Phenotypes; Receptors, Antigen, B-Cell - metabolism; Receptors, IgE - biosynthesis; Signal Transduction; Spleen - cytology; Spleen - immunology; T lymphocytes; Tacrolimus - analogs & derivatives; Tacrolimus - pharmacology; Thionucleotides - pharmacology
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.92.8.3348

Treatment of small resting B cells with soluble F(ab')2fragments 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 (FcεII 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.