The Mertk receptor tyrosine kinase promotes T-B interaction stimulated by IgD B-cell receptor cross-linking.
The Mertk receptor tyrosine kinase facilitates macrophage and DC apoptotic-cell clearance and regulates immune tolerance. Mertk may also contribute to B-cell activation, because Mertk-KO mice fail to develop autoantibodies when allo-activated by T cells. We investigated this possibility with a well-characterized model in which injection of mice with goat anti-IgD antibody causes membrane IgD cross-linking that induces T-independent B cell activation and antigen presentation to T cells. Goat anti-mouse IgD antibody-injected C57BL/6 Mertk-KO mice had normal initial B cell activation and proliferation, but significantly lower T cell activation and proliferation, as well as lower IgE and IgG anti-goat IgG responses, as compared to C57BL/6 WT controls. B cell antigen processing, analyzed by evaluating B cell fluorescence following injection of monoclonal anti-IgD antibody labeled with biotin or FITC, was comparable between Mertk-KO mice and WT mice. IgD Ab primed B cells from Mertk-KO mice exhibited significantly lower ability in activating memory T cells isolated from WT mice injected with the same antigen 10 days before. These observations suggest that Mertk expression is required for optimal B-cell antigen presentation, which is, in turn, required in this model for optimal T cell activation and subsequent T cell-dependent B cell differentiation.
Section of Rheumatology, Department of Medicine, Temple University, 3322 N. Broad St., Philadelphia, PA 19140, USA.
Wen-Hai
WH
Shao
Section of Rheumatology, Department of Medicine, Temple University, 3322 N. Broad St., Philadelphia, PA 19140, USA.
Yuxuan
Y
Zhen
Department of Medicine, Cincinnati Veterans Affairs Medical Center, Cincinnati, OH 45220, USA; Division of Allergy, Immunology and Rheumatology, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA; Division of Immunobiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
Fred D
FD
Finkelman
Section of Rheumatology, Department of Medicine, Temple University, 3322 N. Broad St., Philadelphia, PA 19140, USA. Electronic address: philco@temple.edu.
Philip L
PL
Cohen
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002450:Cell Communication / Q000235:genetics / Q000276:immunology*; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics / Q000276:immunology; D007072:Immunoglobulin D / Q000235:genetics / Q000276:immunology*; D007152:Immunologic Capping / Q000235:genetics / Q000276:immunology; D007156:Immunologic Memory / Q000235:genetics; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000276:immunology*; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000276:immunology*; D011947:Receptors, Antigen, B-Cell / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D000076202:c-Mer Tyrosine Kinase
D007072:Immunoglobulin D; D011518:Proto-Oncogene Proteins; D011947:Receptors, Antigen, B-Cell; C490767:Mertk protein, mouse; D020794:Receptor Protein-Tyrosine Kinases; D000076202:c-Mer Tyrosine Kinase
Ag presentation; IgD cross-linking; Mertk