The CD19/CR2/TAPA-1 complex of B lymphocytes: linking natural to acquired immunity

Annu Rev Immunol. 1995;13:127-49. doi: 10.1146/annurev.iy.13.040195.001015.


B lymphocytes must respond to low concentrations of antigen despite having low affinity antigen receptors during the primary immune response. CD19, a B cell-restricted membrane protein of the immunoglobulin superfamily that associates with the antigen receptor complex, may help the B cell meet this requirement. Cross-linking CD19 to membrane immunoglobulin (mIg) lowers, by two orders of magnitude, the number of mIg that must be ligated to activate phospholipase C (PLC) or to induce DNA synthesis. CD19 is coupled, via protein tyrosine kinases (PTKs), to PLC and phosphatidylinositol 3' kinase (PI3' kinase), and it interacts with the Src-type nonreceptor PTK lyn. It also associates with two other membrane proteins, CR2 (complement receptor type 2, CD21), which permits nonimmunologic ligation of CD19, and TAPA-1, a member of the tetraspan family of membrane proteins. CR2 binds fragments of C3 that are covalently attached to glycoconjugates. This indirectly enables CD19 to be cross-linked to mIg after preimmune recognition of an immunogen by the complement system. CR2 also can be ligated by CD23, a lectin-like membrane protein that resides on cells that may present antigen to B cells. TAPA-1 associates with several other membrane proteins on B and 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 formation of this membrane protein complex by representatives of three different protein families helps the B cell resolve its dilemma of combining broad specificity with high sensitivity.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antigens, CD / genetics
  • Antigens, CD / immunology
  • Antigens, CD19
  • Antigens, Differentiation, B-Lymphocyte / genetics
  • Antigens, Differentiation, B-Lymphocyte / immunology
  • B-Lymphocytes / immunology*
  • Humans
  • Immunity, Innate
  • Membrane Proteins / immunology
  • Mice
  • Molecular Sequence Data
  • Receptors, Complement 3d / immunology
  • Signal Transduction / immunology
  • Tetraspanin 28


  • Antigens, CD
  • Antigens, CD19
  • Antigens, Differentiation, B-Lymphocyte
  • CD81 protein, human
  • Cd81 protein, mouse
  • Membrane Proteins
  • Receptors, Complement 3d
  • Tetraspanin 28