CD40-mediated stimulation of B1 and B2 cells: implication in autoantibody production in murine lupus.
B1 cells usually show preferential responses to T cell-independent antigens. To ask whether B1 cells could respond to CD40-mediated stimulation for proliferation and differentiation, and whether CD40-mediated signals are involved in the production of autoantibodies by B1 cells, we compared responses to our newly established agonistic anti-mouse CD40 monoclonal antibody (mAb) between B1 and B2 cells from autoimmune-prone (NZB x NZW) F1 mice. Stimulation with this mAb induced a similar level of proliferative responses of both B1 and B2 cells, as well as an increase in expression of cell surface molecules I-A, CD54, CD23, CD80, and CD86. While co-stimulation with interleukin (IL)-4 markedly augmented proliferative as well as IgG1 and IgE antibody responses of both B and B2 cells, co-stimulation with IL-5 augmented proliferative and IgM antibody responses of only B1 cells. Splenic B1, but not B2 cells from young (NZB x NZW) F1 mice spontaneously produced substantial amounts of IgM including IgM anti-DNA antibodies, and the levels increased in case of stimulation with anti-CD40 mAb alone, or to a greater extent with the mAb plus IL-4 and IL-5. Collectively, these results indicate that splenic B1 cells from autoimmune (NZB x NZW) F1 mice have a comparable responsiveness to the CD40-mediated stimulation to that of B2 cells, which would be a potent regulatory mechanism involved in the spontaneous production of autoantibodies by B1 cells.
Kaneko
Y
Y
Department of Immunology, Juntendo University School of Medicine, Tokyo, Japan.
Hirose
S
S
Abe
M
M
Yagita
H
H
Okumura
K
K
Shirai
T
T
D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis*; D001402:B-Lymphocytes / Q000187:drug effects* / Q000378:metabolism*; D019013:CD40 Antigens / Q000494:pharmacology*; D002678:Chimera; D005260:Female; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy*; D008213:Lymphocyte Activation / Q000187:drug effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D008814:Mice, Inbred NZB
D001323:Autoantibodies; D019013:CD40 Antigens