title: FCRL5 exerts binary and compartment-specific influence on innate-like B-cell receptor signaling.
abstract: Innate-like splenic marginal zone (MZ) and peritoneal cavity B1 B lymphocytes share critical responsibilities in humoral responses but have divergent B-cell receptor (BCR) signaling features. A discrete marker of these subsets with tyrosine-based dual regulatory potential termed "Fc receptor-like 5" (FCRL5) was investigated to explore this discrepancy. Although FCRL5 repressed the robust BCR activity that is characteristic of MZ B cells, it had no influence on antigen receptor stimulation that is blunted in peritoneal cavity-derived B1 B cells. The molecular basis for the receptor's inhibitory function derived from recruitment of the Src homology-2 domain-containing tyrosine phosphatase 1 (SHP-1) to a cytoplasmic immunoreceptor tyrosine-based inhibitory motif. Surprisingly, mutagenesis of this docking site unearthed coactivation properties for FCRL5 that were orchestrated by independent association of the Lyn Src-family kinase with an intracellular immunoreceptor tyrosine-based activation motif-like sequence. FCRL5's unique binary regulation directly correlated with SHP-1 and Lyn activity, which, like BCR function, differed between MZ and B1 B cells. These findings collectively imply a specialized counterregulatory role for FCRL molecules at the intersection of innate and adaptive immunity.
authors.affiliation: Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
authors.forename: Zilu
authors.initials: Z
authors.lastname: Zhu
authors.forename: Ran
authors.initials: R
authors.lastname: Li
authors.forename: Hao
authors.initials: H
authors.lastname: Li
authors.forename: Tong
authors.initials: T
authors.lastname: Zhou
authors.forename: Randall S
authors.initials: RS
authors.lastname: Davis
mesh_terms: D000818:Animals; D053264:B-Cell Activating Factor / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D017931:DNA Primers / Q000235:genetics; D007113:Immunity, Innate / Q000276:immunology*; D015151:Immunoblotting; D051379:Mice; D018613:Microscopy, Confocal; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism*; D011961:Receptors, Fc / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction / Q000276:immunology*; D013154:Spleen / Q000166:cytology / Q000276:immunology*
chemical_list: D053264:B-Cell Activating Factor; D017931:DNA Primers; C515879:FcRH3 protein, mouse; D011947:Receptors, Antigen, B-Cell; D011961:Receptors, Fc; C505719:TNFSF13B protein, human; D002118:Calcium