Open AccessFcR-Like 2 Inhibition of B Cell Receptor-Mediated Activation of B Cells
Author(s) -
Tanisha Jackson,
Christopher L. Haga,
Götz R. A. Ehrhardt,
Randall S. Davis,
Max D. Cooper
Publication year - 2010
Publication title -
the journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.737
H-Index - 372
eISSN - 1550-6606
pISSN - 0022-1767
DOI - 10.4049/jimmunol.1002305
Subject(s) - protein tyrosine phosphatase , breakpoint cluster region , biology , phosphorylation , proto oncogene tyrosine protein kinase src , immunoreceptor tyrosine based activation motif , microbiology and biotechnology , tyrosine , signal transduction , transmembrane protein , transmembrane domain , tyrosine phosphorylation , cytoplasm , phosphatase , b cell receptor , receptor , sh2 domain , b cell , biochemistry , antibody , genetics
FcR-like (FCRL) 2 is a transmembrane protein with immunomodulatory potential that is preferentially expressed by memory B cells in humans. It has two consensus ITIMs in addition to a putative ITAM sequence in its cytoplasmic domain. We have confirmed the cellular distribution of FCRL2 and analyzed its functional potential to show that coligation with the BCR leads to tyrosine phosphorylation of its ITIM motifs and subsequent Src homology region 2 domain-containing phosphatase-1 recruitment to facilitate inhibition of BCR signaling. Mutational analysis indicates that the tyrosine residues in both inhibitory motifs of FCRL2 are required for complete inhibition of BCR signaling, whereas tyrosines in the putative activation motif are dispensable for signal modulation. These findings suggest a negative immunomodulatory function for FCRL2 in the regulation of memory B cells.
Accelerating Research
Robert Robinson Avenue,
Oxford Science Park, Oxford
OX4 4GP, United Kingdom
Address
John Eccles HouseRobert Robinson Avenue,
Oxford Science Park, Oxford
OX4 4GP, United Kingdom