INDUCTION OF COSTIMULATORY MOLECULES B7-1 AND B7-2 IN MURINE B-CELLS - THE CBA N MOUSE REVEALS A ROLE FOR BRUTONS TYROSINE KINASE IN CD40 MEDIATED B7 INDUCTION/

The binding of CD40 ligand on activated T cells to CD40 on resting B c ells induces the expression of costimulatory molecules B7-1 (CD80) and B7-2 (CD86). The induction of B7 molecules by CD40 ligand-CD40 intera ction represents a critical step in rendering B cells competent for an tigen presentation. The CBA/N mouse has a defect in CD40 signalling wh ich has been attributed to a mutation in Bruton's tyrosine kinase. We have compared the ability of murine CD40 ligand to induce B7-1 and B7- 2 expression on B cells isolated from CBA/N and wild-type CBA/J mice. We find that the CBA/N defect partially impairs both B7-1 and B7-2 ind uction via CD40. Subsequent experiments investigated the roles of diff erent second messenger systems in B7-1 and B7-2 induction in normal B cells. In M12 B lymphomas either CD40 cross-linking or cAMP treatment can induce B7 molecules. Here we report that treatment with dibutyryl- cAMP also induces B7 molecules in normal B cells provided that they ha ve been preactivated by CD40 cross-linking. We also find that PMA and ionomycin treatment of B cells induces B7-2 but not B7-1 expression. O ur data therefore show roles for BTK, cAMP and PMA/ionomycin in B7 ind uction, as well as providing further evidence for differential regulat ion of B7-1 and B7-2 induction in B cells. Copyright (C) 1996 Elsevier Science Ltd.