The development of anti-CD79 monoclonal antibodies for treatment of B-cell neoplastic disease.
The B-cell antigen receptor (BCR) consists of cell surface IgM associated with the CD79 alpha/beta heterodimer. In this paper we describe a panel of monoclonal antibodies (mAbs) recognising the extracellular regions of human CD79 alpha and beta. FACS analysis demonstrated that the mAbs bind to a range of Burkitt's lymphoma lines, a mouse B-cell line (JO-72) transfected with human CD79 alpha and beta, and tumour biopsies from NHL patients. The specificity of the mAbs was confirmed by immunoprecipitation. The Ka for the binding of IgG from the anti-CD79 alpha mAbs to cell surface CD79 alpha on Ramos cells was 3 x 10(8) M-1, and their maximum level of binding, 1.7-2 x 10(5) molecules/cell, matched that obtained with anti-Fc mu and anti-Fd mu mAbs. All four anti-CD79 beta mAbs were of lower affinity. Interestingly, in growth arrest studies, we found that while all anti-Fc mu mAbs caused profound inhibition of proliferation of Ramos cells, a range of other anti-BCR mAbs, which included the anti-CD79, anti-Fab mu, anti-gamma and anti-idiotype reagents, all performed poorly giving a maximum of 25% inhibition. These differences in performance are believed to relate to the ability of anti-BCR mAbs to cross-link neighbouring surface BCR and suggest that, unlike anti-Fc mu which favours cross-linking, most of these mAbs are binding in a monogamous, non-cross-linking, union with the BCR.
Zhang
L
L
Lymphoma Research Unit, Tenovus Laboratory, General Hospital, Southampton, UK.
French
R R
RR
Chan
H T
HT
O'Keefe
T L
TL
Cragg
M S
MS
Power
M J
MJ
Glennie
M J
MJ
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000627:therapeutic use; D000915:Antibody Affinity; D015703:Antigens, CD / Q000276:immunology*; D002051:Burkitt Lymphoma / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D051925:CD79 Antigens; D016466:CHO Cells; D002455:Cell Division / Q000276:immunology; D006224:Cricetinae; D006801:Humans; D051379:Mice; D011233:Precipitin Tests; D011947:Receptors, Antigen, B-Cell / Q000276:immunology*; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D051925:CD79 Antigens; C497881:CD79A protein, human; C497883:CD79B protein, human; C497882:Cd79a protein, mouse; C497884:Cd79b protein, mouse; D011947:Receptors, Antigen, B-Cell