Antibodies to murine CD40 protect normal and malignant B cells from induced growth arrest.
We have previously described the production of polyclonal anti-murine CD40 antibodies that specifically bind recombinant murine CD40 expressed on L cells and induce vigorous proliferation of normal murine B lymphocytes. The current study utilizes these antibodies to explore the distribution and function of CD40 in murine B cell development. Murine CD40 is expressed at high levels by normal splenic B cells and all Ig-positive B cell lymphomas tested to date. It is not expressed by the 70Z/3 pre-B cell line, BaF3 pre-B cell line, or by numerous T cell and myeloid cell lines. 70Z/3 pre-B cells can be induced to express CD40 by LPS stimulation of the cells. Stimulation of purified splenic B cells with anti-CD40 antibodies causes upregulation of class II MHC antigens, CD23, and ICAM-1 and results in extensive aggregation of the cells. Antibodies to murine CD40 are extremely effective at rescuing malignant and normal B cells from induced growth arrest. Anti-CD40 antibodies protect WEHI-231 and CH31 B lymphoma cells from growth arrest induced by soluble anti-IgM antibodies, TGF beta, or a combination of both stimulants. Similarly, anti-IgM preactivated normal splenic B cells which normally die rapidly from growth arrest after 1 or 2 days culture produce a vigorous proliferative response to subsequent stimulation with anti-CD40 antibodies plus IL-4. Interestingly, anti-CD40 antibodies provide little to no protection against B lymphoma growth arrest induced by immobilized anti-IgM antibodies. These data confirm and extend functional properties assigned previously to human CD40 and identify numerous defined murine model systems to explore the molecular basis of CD40-mediated protection from induced B cell growth arrest.
Santos-Argumedo
L
L
DNAX Research Institute, Palo Alto, California 94304.
Gordon
J
J
Heath
A W
AW
Howard
M
M
D000818:Animals; D000906:Antibodies / Q000494:pharmacology*; D000888:Antibodies, Anti-Idiotypic / Q000494:pharmacology; D015703:Antigens, CD / Q000276:immunology* / Q000378:metabolism; D000944:Antigens, Differentiation, B-Lymphocyte / Q000276:immunology* / Q000378:metabolism; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D019013:CD40 Antigens; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002455:Cell Division; D002460:Cell Line; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D066298:In Vitro Techniques; D018799:Intercellular Adhesion Molecule-1; D008213:Lymphocyte Activation; D016393:Lymphoma, B-Cell / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D051381:Rats; D017455:Receptors, IgE / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000276:immunology
D000906:Antibodies; D000888:Antibodies, Anti-Idiotypic; D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; D019013:CD40 Antigens; D015815:Cell Adhesion Molecules; D000949:Histocompatibility Antigens Class II; D017455:Receptors, IgE; D018799:Intercellular Adhesion Molecule-1