Identification of CD72 as a lymphocyte receptor for the class IV semaphorin CD100: a novel mechanism for regulating B cell signaling

Immunity. 2000 Nov;13(5):621-31. doi: 10.1016/s1074-7613(00)00062-5.


We have identified the lymphocyte semaphorin CD100/Sema4D as a CD40-inducible molecule by subtractive cDNA cloning. CD100 stimulation significantly enhanced the effects of CD40 on B cell responses. Administration of soluble CD100 markedly accelerated in vivo antigen-specific antibody responses. CD100 receptors with different binding affinities were detected on renal tubular cells (K(d) = approximately 1 x 10(-9)M) and lymphocytes (K(d) = approximately 3 x 10(-7)M). Expression cloning revealed that the CD100 receptor on lymphocytes is CD72, a negative regulator of B cell responsiveness. CD72 thus represents a novel class of semaphorin receptors. CD100 stimulation induced tyrosine dephosphorylation of CD72 and dissociation of SHP-1 from CD72. Our findings indicate that CD100 plays a critical role in immune responses by the novel mechanism of turning off negative signaling by CD72.

Publication types

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

MeSH terms

  • Animals
  • Antigens, CD / immunology*
  • Antigens, Differentiation, B-Lymphocyte / immunology*
  • B-Lymphocytes / immunology*
  • CHO Cells
  • Cricetinae
  • Membrane Glycoproteins / immunology*
  • Receptors, Immunologic / immunology*
  • Semaphorins*
  • Signal Transduction / immunology*


  • Antigens, CD
  • Antigens, Differentiation, B-Lymphocyte
  • CD100 antigen
  • CD72 protein, human
  • Membrane Glycoproteins
  • Receptors, Immunologic
  • Semaphorins