Predominant Expression and Activation-Induced Tyrosine Phosphorylation of Phospholipase C-γ2 in B Lymphocytes

• Published in: Proceedings of the National Academy of Sciences - PNAS 1992-06, Vol.89 (12), p.5660-5664
• Main Authors: Coggeshall, K. Mark, McHugh, Joan C., Altman, Amnon
• Format: Article
• Language: English
• Subjects: Analysis of the immune response. Humoral and cellular immunity; Antibodies; B lymphocytes; Biological and medical sciences; Cell lines; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Immunobiology; Inositols; Lymphocytes; Mice; Organs and cells involved in the immune response; Phosphorylation; Protein isoforms; Receptors; T lymphocytes
• ISSN: 0027-8424; 1091-6490

The triggering of T- or B-cell antigen-specific receptors is accompanied by rapid tyrosine phosphorylation of distinct cellular substrates, one of which is the γ1 isoform of inositol phospholipid-specific phospholipase C (PLC-γ1). This phosphorylation event, mediated by a putative protein tyrosine kinase coupled to the antigen receptor, probably stimulates the enzymatic activity of PLC-γ1, thereby promoting inositol phospholipid hydrolysis and other downstream signal transduction events. Recently, another ubiquitously expressed PLC isoform, PLC-γ2 (which shares 50.2% amino acid homology with PLC-γ1), has been identified. PLC-γ2-specific antibodies were used to evaluate the distribution and potential signaling role of this isoform in lymphocytes. Here, we report that, in contrast to T lymphocytes that express predominantly PLC-γ1, the major isoform expressed in murine and human resting B cells is PLC-γ2. Among B-cell tumor lines, all five murine B-lymphoma lines tested and one of six human B-lymphoblastoid cell lines also expressed predominantly PLC-γ2. However, three other human lines preferentially expressed PLC-γ1, and two others displayed similar levels of the two PLC-γ isoforms. Furthermore, the triggering of B-cell surface immunoglobulin by anti-receptor antibodies was accompanied by a rapid tyrosine phosphorylation of PLC-γ2, which peaked after 5 min of stimulation. Conversely, and in agreement with recent reports, triggering of the T-cell antigen receptor complex led to the predominant phosphorylation of PLC-γ1 on tyrosine. These findings identify PLC-γ2 as a substrate for a B-cell putative protein tyrosine kinase coupled to the antigen receptor and suggest that its tyrosine phosphorylation constitutes a critical and early event in B-cell activation and, furthermore, that PLC-γ1 and PLC-γ2 may participate in similar but distinct signal transduction pathways in lymphocytes.