Author ORCID Identifier
Document Type
Article
Publication Date
10-1-2014
Publication Title
PLOS ONE
Volume
9
Issue
10
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 PCor 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.
Recommended Citation
Martinez-Torres F, Nochi T, Wahl A, Garcia JV, Denton PW (2014) Hypogammaglobulinemia in BLT Humanized Mice – An Animal Model of Primary Antibody Deficiency. PLoS ONE 9(10): e108663. doi:10.1371/journal.pone.0108663
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Comments
© 2014 Martinez-Torres et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.