title: Plexin-D1 is a novel regulator of germinal centers and humoral immune responses.
abstract: Long-lived humoral immune responses depend upon the generation of memory B cells and long-lived plasma cells during the germinal center (GC) reaction. These memory compartments, characterized by class-switched IgG and high-affinity Abs, are the basis for successful vaccination. We report that a new member of the plexin family of molecules, plexin-D1, controls the GC reaction and is required for secondary humoral immune responses. Plexin-D1 was not required for B cell maturation, marginal zone precursor development, dark and light zone formation, Igλ(+) and Igκ(+) B cell skewing, B1/B2 development, and the initial extrafollicular response. Plexin-D1 expression was increased following B cell activation, and PlxnD1(-/-) mice exhibited defective GC reactions during T-dependent immune activation. PlxnD1(-/-) B cells showed a defect in migration toward the GC chemokines, CXCL12, CXCL13, and CCL19. Accordingly, PlxnD1(-/-) mice exhibited defective production of IgG1 and IgG2b, but not IgG3 serum Ab, accompanied by reductions in long-lived bone marrow plasmacytes and recall humoral memory responses. These data show a new role for immune plexins in the GC reaction and generation of immunologic memory.
authors.affiliation: Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, NC 27599, USA.
authors.forename: Eda K
authors.initials: EK
authors.lastname: Holl
authors.forename: Brian P
authors.initials: BP
authors.lastname: O'Connor
authors.forename: T Matt
authors.initials: TM
authors.lastname: Holl
authors.forename: Kelly E
authors.initials: KE
authors.lastname: Roney
authors.forename: Albert G
authors.initials: AG
authors.lastname: Zimmermann
authors.forename: Sushmita
authors.initials: S
authors.lastname: Jha
authors.forename: Garnett
authors.initials: G
authors.lastname: Kelsoe
authors.forename: Jenny P-Y
authors.initials: JP
authors.lastname: Ting
mesh_terms: D000818:Animals; D016175:B-Lymphocyte Subsets / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D054415:Chemokine CCL19 / Q000172:deficiency / Q000378:metabolism; D054377:Chemokine CXCL12 / Q000172:deficiency / Q000378:metabolism; D054382:Chemokine CXCL13 / Q000172:deficiency / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D018858:Germinal Center / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D056724:Immunity, Humoral; D017578:Immunoglobulin Class Switching; D007074:Immunoglobulin G / Q000096:biosynthesis* / Q000097:blood / Q000276:immunology; D007156:Immunologic Memory; D047908:Intracellular Signaling Peptides and Proteins; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology*; D010950:Plasma Cells / Q000276:immunology
chemical_list: C515461:Ccl19 protein, mouse; D054415:Chemokine CCL19; D054377:Chemokine CXCL12; D054382:Chemokine CXCL13; C515256:Cxcl12 protein, mouse; C486386:Cxcl13 protein, mouse; D007074:Immunoglobulin G; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; C473552:Plxnd1 protein, mouse