title: A disintegrin and metalloproteinase 10 regulates antibody production and maintenance of lymphoid architecture.
abstract: A disintegrin and metalloproteinase 10 (ADAM10) is a zinc-dependent proteinase related to matrix metalloproteinases. ADAM10 has emerged as a key regulator of cellular processes by cleaving and shedding extracellular domains of multiple transmembrane receptors and ligands. We have developed B cell-specific ADAM10-deficient mice (ADAM10(B-/-)). In this study, we show that ADAM10 levels are significantly enhanced on germinal center B cells. Moreover, ADAM10(B-/-) mice had severely diminished primary and secondary responses after T-dependent immunization. ADAM10(B-/-) displayed impaired germinal center formation, had fewer follicular Th cells, decreased follicular dendritic cell networks, and altered chemokine expression in draining lymph nodes (LNs). Interestingly, when spleen and LN structures from immunized mice were analyzed for B and T cell localization, tissues structure was aberrant in ADAM10(B-/-) mice. Importantly, when ADAM10-deficient B cells were stimulated in vitro, they produced comparable Ab as wild type B cells. This result demonstrates that the defects in humoral responses in vivo result from inadequate B cell activation, likely because of the decrease in follicular Th cells and the changes in structure. Thus, ADAM10 is essential for the maintenance of lymphoid structure after Ag challenge.
authors: Department of Microbiology and Immunology, Virginia Commonwealth University School of Medicine, Richmond, VA 23298, USA.
authors: Natalia S
authors: NS
authors: Chaimowitz
authors: Rebecca K
authors: RK
authors: Martin
authors: Joanna
authors: J
authors: Cichy
authors: David R
authors: DR
authors: Gibb
authors: Pooja
authors: P
authors: Patil
authors: Dae-Joong
authors: DJ
authors: Kang
authors: Julie
authors: J
authors: Farnsworth
authors: Eugene C
authors: EC
authors: Butcher
authors: Brent
authors: B
authors: McCright
authors: Daniel H
authors: DH
authors: Conrad
mesh_terms: D051722:ADAM Proteins / Q000096:biosynthesis / Q000172:deficiency / Q000502:physiology*; D000072197:ADAM10 Protein; D053829:Amyloid Precursor Protein Secretases / Q000096:biosynthesis / Q000172:deficiency / Q000502:physiology*; D000818:Animals; D016175:B-Lymphocyte Subsets / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D016466:CHO Cells; D006224:Cricetinae; D018858:Germinal Center / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D056724:Immunity, Humoral / Q000235:genetics; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D008565:Membrane Proteins / Q000096:biosynthesis / Q000172:deficiency / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010581:Peyer's Patches / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000201:enzymology / Q000276:immunology; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology
chemical_list: D008565:Membrane Proteins; D053829:Amyloid Precursor Protein Secretases; D051722:ADAM Proteins; D000072197:ADAM10 Protein; C491234:Adam10 protein, mouse