FcR-like 2 Inhibition of B cell receptor-mediated activation of B cells

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 i...

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Bibliographic Details
Published in:The Journal of immunology (1950) 2010-12, Vol.185 (12), p.7405-7412
Main Authors: Jackson, Tanisha A, Haga, Christopher L, Ehrhardt, Götz R A, Davis, Randall S, Cooper, Max D
Format: Article
Language:English
Subjects:
Amino Acid Motifs
Amino Acid Substitution
Animals
B-Lymphocytes - immunology
Cell Line
Humans
Immunologic Memory - physiology
Lymphocyte Activation - immunology
Mice
Mutation
Phosphorylation - genetics
Phosphorylation - immunology
Protein Structure, Tertiary
Receptors, Antigen, B-Cell - genetics
Receptors, Antigen, B-Cell - immunology
Receptors, Cell Surface - genetics
Receptors, Cell Surface - immunology
Signal Transduction - genetics
Signal Transduction - immunology
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Summary: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.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.1002305