A monoclonal antibody against a murine CD38 homologue delivers a signal to 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 look for a cell-surface molecule that delivered a signal regulating apoptotic cell death of B cells. Because spleen cells in resting culture die 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 only prolonged spleen cell survival in vitro, but also protected spleen cells from apoptotic cell death brought about by irradiation or dexamethasone. Moreover, stimulation of spleen cells with CS/2 mAb induced changes of cells to blastoid morphology, and a significant uptake of [3H]thymidine ([3H]TdR). The antigen recognized by CS/2 mAb (CS/2 Ag) was expressed on preB cells, B cells, and Mac-1+ cells. The cells surviving in vitro culture or irradiation in response to ligation with CS/2 mAb were mostly B cells expressing the CS/2 Ag. In addition, B cells 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 that 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 CS/2 mAb is directed against a murine CD38 homologue, and suggest a possible role of the murine CD38 homologue in controlling apoptotic cell death of B cells.
Yamashita
Y
Y
Department of Immunology, Saga Medical School, Japan.
Miyake
K
K
Kikuchi
Y
Y
Takatsu
K
K
Noda
S
S
Kosugi
A
A
Kimoto
M
M
D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism*; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000235:genetics / Q000276:immunology*; D017209:Apoptosis / Q000276:immunology*; D001402:B-Lymphocytes / Q000166:cytology* / Q000187:drug effects / Q000528:radiation effects; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology; D005720:Gamma Rays; D008562:Membrane Glycoproteins; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009699:N-Glycosyl Hydrolases / Q000235:genetics / Q000276:immunology*; D051381:Rats; D017208:Rats, Wistar; D013154:Spleen / Q000166:cytology
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000943:Antigens, Differentiation; D008562:Membrane Glycoproteins; D003907:Dexamethasone; D009699:N-Glycosyl Hydrolases; D036541:ADP-ribosyl Cyclase; C498155:Cd38 protein, mouse; C498156:Cd38 protein, rat; D051997:ADP-ribosyl Cyclase 1