INDUCTION BY ANTI-CD40 ANTIBODY OR SOLUBLE CD40 LIGAND AND CYTOKINES OF IGG, IGA AND IGE PRODUCTION BY B-CELLS FROM PATIENTS WITH X-LINKED HYPER-IGM SYNDROME

We studied the ability of B lymphocytes from patients with X-linked hy per IgM syndrome (HIGM1) to be activated via the CD40 membrane recepto r. HIGM1 is caused by a CD40 ligand gene mutation, leading to defectiv e expression on the membrane of activated T lymphocytes. We found that triggering of B cells by an anti-CD40 monoclonal antibody or the solu ble CD40 ligand plus interleukin (IL)-4 or IL-10 led to B cell prolife ration and/or differentiation towards IgG, IgA and IgE secretion. This was reflected by transcription of Cgamma, alpha and epsilon membrane isotype expression and IgG, IgA and IgE production. These results conf irm the integrity of B cells in patients with the HIGM1 immunodeficien cy and open up new therapeutic possibilities.