Differential expression of inducible costimulator-ligand splice variants: Lymphoid regulation of mouse GL50-B and human GL50 molecules

The process of immunological costimulation between APC and T cells is media ted by protein ligand:receptor interactions. To date, costimulatory recepto rs known to be expressed by T cells include the structurally related protei ns CD28 and the inducible costimulator (ICOS). The ligands to human and mou se ICOS, human GL50 (hGL50), and mouse GL50 (mGL50) were recently cloned an d demonstrated to have sequence similarity to the CD28 ligands B7-1 and B7- 2. Examination of mGL50 cDNA transcripts by 3 ' RACE revealed an alternativ ely spliced form, mGL50-B, that encoded a protein product with a divergent 27-aa intracellular domain. Both mGL50- and mGL50-B-transfected cells exhib ited binding to human and mouse ICOS-Ig fusion protein, indicating that the alternate cytoplasmic domain of mGL50-B does not interfere with extracellu lar interactions with ICOS receptor. Flow cytometric and RT-PCR analysis of BALB/c and RAG1(-/-) mice splenocytes demonstrate that freshly isolated B cells, T cells, macrophages, and dendritic cells express both splice varian t forms of ICOS ligand. Comparative analyses with the human ICOS ligand spl ice variants hGL50 and B7-H2 indicate that differential splicing at the jun ction of cytoplasmic exon 6 and exon 7 may be a common method by which GL50 -ICOS immunological costimulatory processes are regulated in vivo.