CD40 stimulation promotes human secondary immunoglobulin responses in HuPBL-SCID chimeras

Antibodies to CD40 have been demonstrated to promote B-cell, growth and dif ferentiation in vitro. In order to determine if CD40 stimulation could prom ote antigen-specific human immunoglobulin (Ig) production in vivo we examin ed the effects of anti-human CD40 MoAb in an in vivo system where human per ipheral blood lymphocytes (huPBL) were engrafted into mice with severe comb ined immune deficiency (SCID). The huPBL-SCID mice were then given various doses of diphtheria-tetanus toroid (DT) vaccine and were examined for the p resence of human DT-specific antibodies by ELISA. Surprisingly treatment wi th anti-CD40 significantly lowered background DT responses versus untreated chimeras in unimmunized huPBL-SCID mice. However, after immunization, huPB L-SCID mice treated with anti-CDBO MoAb responded to a significantly greate r extent in response 60 the vaccine compared with control huPBL-SCID mice, although total Ig levels were sometimes lower in anti-CD40-treated mice. Th e predominant Ig isotype induced after immunization was IgG. Thus, CD40 sti mulation promotes human secondary IgG responses in huPBL-SCID mice. These d ata demonstrate that CD40 stimulation is capable of promoting antigen-speci fic human B-cell responses in vice. (C) 1999 Academic Press.