Alternative splicing of CD45 pre-mRNA is uniquely obedient to conditions in lymphoid cells

The leucocyte common antigen (LCA or CD45) consists of various isoforms gen erated by alternative splicing of variable exons 4, 5 and 6 (or A, B and C) . To follow splicing behaviour in different cell types we developed a human CD45 mini-gene and analysed its expression in transfected cell lines and t ransgenic mouse tissues. In Cos-l, HeLa and 3T3 cells we found distinct exp ression patterns which could only be modulated slightly by protein synthesi s inhibitors but not by variation in culture conditions like pH, serum conc entration and cell density, or by stimulation with phorbol ester (TPA). In all nonlymphoid transgenic tissues the default splicing pattern (CD45R0) wa s found, while the expression profile in lymphoid cells, where all eight is oforms are present, mimics that of the endogenous mouse LCA gene products. Next, to examine the factors involved in alternative exon use we analysed t he expression pattern of members of the family of SR proteins, well known s plicing regulators with arginine/serine-rich (R/S) domains. Cell lines expr essed variable levels of SRp75, SRp30 and SRp20 and constant amounts of SRp 40. Mouse tissues expressed large amounts of SRp75, SRp55 and SRp40, additi onal expression of SRp30s and SRp20 was restricted to lymphoid tissues. The refore, SRp30 and SRp20 may contribute to forming the appropriate cellular conditions for alternative use of CD45 exons 4-6 in the haematopoietic comp artment. (C) 1999 Elsevier Science B.V. All rights reserved.