L. Santosargumedo et al., ANTIBODIES TO MURINE CD40 PROTECT NORMAL AND MALIGNANT B-CELLS FROM INDUCED GROWTH ARREST, Cellular immunology, 156(2), 1994, pp. 272-285
We have previously described the production of polyclonal anti-murine
CD40 antibodies that specifically bind recombinant murine CD40 express
ed on L cells and induce vigorous proliferation of normal murine B lym
phocytes. The current study utilizes these antibodies to explore the d
istribution 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 7
0Z/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 b
y LPS stimulation of the cells. Stimulation of purified splenic B cell
s with anti-CD40 antibodies causes upregulation of class II MHC antige
ns, CD23, and ICAM-1 and results in extensive aggregation of the cells
. Antibodies to murine CD40 are extremely effective at rescuing malign
ant and normal B cells from induced growth arrest. Anti-CD40 antibodie
s protect WEHI-231 and CH31 B lymphoma cells from growth arrest induce
d by soluble anti-IgM antibodies, TGF beta, or a combination of both s
timulants. Similarly, anti-IgM preactivated normal splenic B cells whi
ch normally die rapidly from growth arrest after 1 or 2 days culture p
roduce a vigorous proliferative response to subsequent stimulation wit
h anti-CD40 antibodies plus IL-4. Interestingly, anti-CD40 antibodies
provide little to no protection against B lymphoma growth arrest induc
ed by immobilized anti-IgM antibodies. These data confirm and extend f
unctional properties assigned previously to human CD40 and identify nu
merous defined murine model systems to explore the molecular basis of
CD40-mediated protection from induced B cell growth arrest. (C) 1994 A
cademic Press, Inc.