Suppression of apoptosis in normal and neoplastic human B lymphocytes by CD40 ligand is independent of Bc1-2 induction.

Abstract:

:The tendency of isolated germinal center (GC) B cells to undergo apoptosis was suppressed by recombinant cell-bound CD40 ligand (CD40L): after 2 days at 37 degrees C, > 80% of cells remained viable in the presence of CD40L as compared to < 1% in control cultures. CD40L sustained a high rate of DNA synthesis in GC cells and was more effective than monoclonal antibody to CD40 in this regard. Group I Burkitt lymphoma (BL) cell lines induced to undergo apoptosis with anti-immunoglobulin or calcium ionophore were also protected by CD40L. In BL cells, this route of rescue was not accompanied by induction of Bc1-2 protein, the expression of which has been linked to hemopoietic cell survival. Bc1-2 was induced in GC cells responding to CD40L, but its appearance was a relatively late event not reaching significant levels over controls until day 2 of culture. Thus induction of Bc1-2 appears to be secondary to the survival signal imparted by CD40L. These findings are discussed in relation to a potential role for CD40L in supporting B cell tumors in vivo and the discovery that the molecular defect in the X-linked Hyper-IgM syndrome is targeted to the CD40L gene.

journal_name

Eur J Immunol

authors

Holder MJ,Wang H,Milner AE,Casamayor M,Armitage R,Spriggs MK,Fanslow WC,MacLennan IC,Gregory CD,Gordon J

doi

10.1002/eji.1830230948

subject

Has Abstract,Author List Incomplete

pub_date

1993-09-01 00:00:00

pages

2368-71

issue

9

eissn

0014-2980

issn

1521-4141

journal_volume

23

pub_type

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