THE STRUCTURE OF AN ALTERNATE FORM OF COMPLEMENT C3 THAT DISPLAYS COSTIMULATORY GROWTH-FACTOR ACTIVITY FOR B-LYMPHOCYTES

In this study, the structure of a novel 1.9-kb transcript coding for c omplement component 3 (C3) is described. This alternate C3 is identica l to the 3' end of the C3 message beginning at position 3300 of the C3 cDNA. Its transcription appears to be driven by an alternate promoter located within intron 8 of the C3 gene. This alternate C3 message con tains an open reading frame that may encode a 536-amino acid-long prot ein identical to the 3' part of the C3 alpha chain. The resulting prot ein contains the complement receptor CR2 binding site. The suggested 5 ' end of coding region of the alternate C3 includes information for a potential hydrophobic leader peptide that would allow secretion of the protein. In vitro assays with macrophage-depleted mouse splenic B cel ls indicate that an activity is secreted from cell lines transfected w ith the alternate C3 cDNA. Together with Sepharose-bound immunoglobuli n M-specific monoclonal antibodies and interleukin 2, it costimulates the proliferation of B cells. Implications for possible in vivo functi ons are discussed.