Cloning, expression and biological function of the bovine CD40 homologue: Role in B-lymphocyte growth and differentiation in cattle

Members of the tumour necrosis factor receptor superfamily play a key role in B-lymphocyte survival, proliferation, differentiation and programmed cell death. A member of this superfamily, the CD40 molecule, plays an important role in the differentiation of B lymphocytes into effector cells and in early activation through cognate interaction with T lymphocytes. In this report, we describe a cDNA and its protein product identified in cattle with approximately 70% sequence conservation at the nucleic acid level with the human CD40 gene. Transcripts for the boCD40 molecule were identified in resting and activated B lymphocytes, some but not all CD4(+) and CD8(+) T lymphocyte clones, and peripheral blood-derived T lymphocytes. Coculture of resting B cells with simian virus 40 (SV40)-transformed NIH3T3 (MOP8) cells stably transfected with the ligand for CD40 (bovine CD40 ligand, boCD40L), resulted in proliferation which was enhanced by addition of rbo interleukin-4 (IL-4). Cross-linkage of CD40 on bovine B lymphocytes upon coculture with CD40L-transfected cells resulted in the increased production of secretory IgM and, to a lesser extent, of IgG. Addition of rboIL-4 to these cultures increased levels of IgM and IgG secretion approximately twofold over those induced by CD40L alone. Our results indicate that many of the functions described for human and mouse CD40 are also conserved in the bovine but that differences in subset distribution of expression of the CD40 molecule in lymphoid cell types in cattle may impact on regulation of the early activation steps in the acquired immune response.