CD40-mediated stimulation of B1 and B2 cells: implication in autoantibody production in murine lupus

Eur J Immunol. 1996 Dec;26(12):3061-5. doi: 10.1002/eji.1830261236.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autoantibodies / biosynthesis*
  • B-Lymphocytes / drug effects*
  • B-Lymphocytes / metabolism*
  • CD40 Antigens / pharmacology*
  • Chimera
  • Female
  • Lupus Erythematosus, Systemic / drug therapy*
  • Lymphocyte Activation / drug effects*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred NZB


  • Autoantibodies
  • CD40 Antigens