THE CD19 CR2/TAPA-1 COMPLEX OF B-LYMPHOCYTES - LINKING NATURAL TO ACQUIRED-IMMUNITY/

B lymphocytes must respond to low concentrations of antigen despite ha ving low affinity antigen receptors during the primary immune response . CD19, a B cell-restricted membrane protein of the immunoglobulin sup erfamily that associates with the antigen receptor complex, may help t he B cell meet this requirement. Cross-linking CD19 to membrane immuno globulin (mig) lowers, by two orders of magnitude, the number of mig t hat must be ligated to activate phospholipase C (PLC) or to induce DNA synthesis. CD19 is coupled, via protein tyrosine kinases (PTKs), to P LC and phosphatidylinositol 3' kinase (PI3' kinase), and it interacts with the Src-type nonreceptor PTK Iyn. It also associates with two oth er membrane proteins, CR2 (complement receptor type 2, CD21), which pe rmits nonimmunologic ligation of CD19, and TAPA-1, a member of the tet raspan family of membrane proteins. CR2 binds fragments of C3 that are covalently attached to glycoconjugates. This indirectly enables CD19 to be crosslinked to mig after preimmune recognition of an immunogen b y the complement system. CR2 also can be ligated by CD23, a lectin-lik e membrane protein that resides on cells that may present antigen to B cells. TAPA-1 associates with several other membrane proteins on B an d T cells, including MHC class II, CD4, and CD8, and it promotes Ca2+- and LFA-1-independent homotypic aggregation when ligated directly or indirectly through CD19 or CR2. This may facilitate interaction of the B cell with other cells essential for cellular activation. The format ion of this membrane protein complex by representatives of three diffe rent protein families helps the B cell resolve its dilemma of combinin g broad specificity with high sensitivity.