Journal
JOURNAL OF CLINICAL INVESTIGATION
Volume 132, Issue 2, Pages -Publisher
AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/JCI150985
Keywords
-
Categories
Funding
- National Institute of Child Health and Human Development [5R24HD000836]
- AbbVie
- National Institute of Allergy and Infectious Diseases (NIAID), NIH [U19 AI082724]
- Gruber Science Foundation
- Richard K. Gershon fellowship from the Department of Immunobiology at Yale University
- Philippe Foundation
Ask authors/readers for more resources
Using humanized mouse models, it was observed that there is a strong skewing of the expressed immunoglobulin repertoire upon transit into the peripheral naive B cell pool. Positive selection of expanded naive B cells is beneficial, while negative selection of autoreactive B cells requires the involvement of regulatory T cells.
Although negative selection of developing B cells in the periphery is well described, yet poorly understood, evidence of naive B cell positive selection remains elusive. Using 2 humanized mouse models, we demonstrate that there was strong skewing of the expressed immunoglobulin repertoire upon transit into the peripheral naive B cell pool. This positive selection of expanded naive B cells in humanized mice resembled that observed in healthy human donors and was independent of autologous thymic tissue. In contrast, negative selection of autoreactive B cells required thymus-derived Tregs and MHC class II-restricted self antigen presentation by B cells. Indeed, both defective MHC class II expression on B cells of patients with rare bare lymphocyte syndrome and prevention of self-antigen presentation via HLA-DM inhibition in humanized mice resulted in the production of autoreactive naive B cells. These latter observations suggest that Tregs repressed autoreactive naive B cells continuously produced by the bone marrow. Thus, a model emerged, in which both positive and negative selection shaped the human naive B cell repertoire and that each process was mediated by fundamentally different molecular and cellular mechanisms.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available