A MONOCLONAL-ANTIBODY AGAINST A MURINE CD38 HOMOLOG DELIVERS A SIGNALTO B-CELLS FOR PROLONGATION OF SURVIVAL AND PROTECTION AGAINST APOPTOSIS IN-VITRO - UNRESPONSIVENESS OF X-LINKED IMMUNODEFICIENT B-CELLS

A novel monoclonal antibody (mAb) was established in an attempt to loo k for a cell-surface molecule that delivered a signal regulating apopt otic cell death of B cells, Because spleen cells in resting culture di e from apoptosis, mAb were looked for that were able to prolong spleen cell survival in vitro. This screening selected mAb CS/2. CS/2 not on ly prolonged spleen cell survival in vitro, but also protected spleen cells from apoptotic cell death brought about by irradiation or dexame thasone. Moreover, stimulation of spleen cells with CS/2 mAb induced c hanges of cells to blastoid morphology, and a significant uptake of [H -3]thymidine ([H-3]TdR). The antigen recognized by CS/2 mAb (CS/2 Ag) was expressed on preB cells. B cells, and Mac-lt cells, The cells surv iving and vitro culture or irradiation in response to ligation with CS /2 mAb were mostly B cells expressing the CS/2 Ag, In addition, B cell s from X-linked immunodeficient (XID) mice did not respond to CS/2 mAb . These results indicate that CS/2 mAb is agonistic to B cells, and th at XID mice are deficient in this CS/2 mAb-mediated activation pathway . Determination of the amino-terminal 24 amino acid residues revealed that the CS/2 Ag appears to be identical to the murine CD38 homologue, These results are consistent with the conclusion that CS/2 mAb is dir ected against a murine CD38 homologue, and suggest a possible role of the murine CD38 homologue in controlling apoptotic cell death of B cel ls.