title: Hypogammaglobulinemia in BLT humanized mice--an animal model of primary antibody deficiency.
abstract: Primary antibody deficiencies present clinically as reduced or absent plasma antibodies without another identified disorder that could explain the low immunoglobulin levels. Bone marrow-liver-thymus (BLT) humanized mice also exhibit primary antibody deficiency or hypogammaglobulinemia. Comprehensive characterization of B cell development and differentiation in BLT mice revealed other key parallels with primary immunodeficiency patients. We found that B cell ontogeny was normal in the bone marrow of BLT mice but observed an absence of switched memory B cells in the periphery. PC-KLH immunizations led to the presence of switched memory B cells in immunized BLT mice although plasma cells producing PC- or KLH- specific IgG were not detected in tissues. Overall, we have identified the following parallels between the humoral immune systems of primary antibody deficiency patients and those in BLT mice that make this in vivo model a robust and translational experimental platform for gaining a greater understanding of this heterogeneous array of humoral immunodeficiency disorders in humans: (i) hypogammaglobulinemia; (ii) normal B cell ontogeny in bone marrow; and (iii) poor antigen-specific IgG response to immunization. Furthermore, the development of strategies to overcome these humoral immune aberrations in BLT mice may in turn provide insights into the pathogenesis of some primary antibody deficiency patients which could lead to novel clinical interventions for improved humoral immune function.
authors.affiliation: Division of Infectious Diseases, Department of Medicine, UNC Center for AIDS Research, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina, United States of America.
authors.forename: Francisco
authors.initials: F
authors.lastname: Martinez-Torres
authors.affiliation: Division of Infectious Diseases, Department of Medicine, UNC Center for AIDS Research, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina, United States of America.
authors.forename: Tomonori
authors.initials: T
authors.lastname: Nochi
authors.affiliation: Division of Infectious Diseases, Department of Medicine, UNC Center for AIDS Research, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina, United States of America.
authors.forename: Angela
authors.initials: A
authors.lastname: Wahl
authors.affiliation: Division of Infectious Diseases, Department of Medicine, UNC Center for AIDS Research, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina, United States of America.
authors.forename: J Victor
authors.initials: JV
authors.lastname: Garcia
authors.affiliation: Division of Infectious Diseases, Department of Medicine, UNC Center for AIDS Research, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina, United States of America.
authors.forename: Paul W
authors.initials: PW
authors.lastname: Denton
mesh_terms: D000361:Agammaglobulinemia / Q000276:immunology*; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D001853:Bone Marrow / Q000276:immunology*; D004195:Disease Models, Animal; D064593:Heterografts; D006801:Humans; D007136:Immunoglobulins / Q000097:blood / Q000276:immunology; D007156:Immunologic Memory; D008099:Liver / Q000276:immunology*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008822:Mice, Transgenic; D013950:Thymus Gland / Q000276:immunology*
chemical_list: D007136:Immunoglobulins