CD84 is up-regulated on a major population of human memory B cells and recruits the SH2 domain containing proteins SAP and EAT-2.
CD84 is a member of the CD2 subset of the immunoglobulin superfamily of cell surface receptors. Several members of this family are involved in the activation of T cells and NK cells. Although CD84 was originally cloned from a human B cell line cDNA library, very little is known regarding its biology on primary human leukocytes. We investigated the expression and biochemistry of CD84 on human B cells. CD84 was expressed on B cells in peripheral blood, spleen and cord blood. Two populations of splenic B cells could be resolved, CD84(lo) and CD84(hi). CD84(hi) B cells represented a subset of memory B cells as demonstrated by increased cell size, co-expression of the memory B cell-specific marker CD27, somatically mutated Ig variable region genes, and increased proliferation compared to CD84(lo) B cells. CD84 became rapidly phosphorylated on tyrosine residues following ligation with a specific monoclonal antibody and recruited the cytoplasmic adaptor proteins SAP and EAT-2. The ability of CD84 to undergo tyrosine phosphorylation and to recruit these SH2 domain-containing proteins suggests it may function in the activation of B cells, particularly memory cells, and its signal transduction pathway may utilize SAP and/or EAT-2. Thus, investigation of expression and function of CD84 and CD27 is likely to contribute to a greater understanding of the development and biology of memory B cells in normal and immunocompromised hosts.
Immune Regulation Group, Centenary Institute for Cancer Medicine and Cell Biology, Newtown, Australia. s.tangye@centenary.usyd.edu.au
Stuart G
SG
Tangye
Barbara C M
BC
van de Weerdt
Danielle T
DT
Avery
Philip D
PD
Hodgkin
D000595:Amino Acid Sequence; D015703:Antigens, CD / Q000032:analysis / Q000502:physiology*; D001402:B-Lymphocytes / Q000502:physiology*; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism*; D002460:Cell Line; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000235:genetics; D007156:Immunologic Memory; D047908:Intracellular Signaling Peptides and Proteins; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins; D008969:Molecular Sequence Data; D010766:Phosphorylation; D000071179:Signaling Lymphocytic Activation Molecule Associated Protein; D000071176:Signaling Lymphocytic Activation Molecule Family; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism; D015854:Up-Regulation; D018909:src Homology Domains
D015703:Antigens, CD; C498970:CD84 protein, human; D002352:Carrier Proteins; D007135:Immunoglobulin Variable Region; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; C114953:SH2D1A protein, human; C103572:SH2D1B protein, human; D000071179:Signaling Lymphocytic Activation Molecule Associated Protein; D000071176:Signaling Lymphocytic Activation Molecule Family; D014157:Transcription Factors; D014443:Tyrosine