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J Immunol. 2018 Aug 15;201(4):1229-1240. doi: 10.4049/jimmunol.1800162. Epub 2018 Jul 13.

IL-7 Enables Antibody Responses to Bacterial Polysaccharides by Promoting B Cell Receptor Diversity.

Author information

1
Department of Microbiology and Immunology, Sidney Kimmel Medical College, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107; and.
2
Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294.
3
Department of Microbiology and Immunology, Sidney Kimmel Medical College, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107; and kishore.alugupalli@jefferson.edu.

Abstract

Polysaccharide vaccines such as the Vi polysaccharide (ViPS) of Salmonella enterica serovar Typhi induce efficient Ab responses in adults but not in young children. The reasons for this difference are not understood. IL-7 dependency in B cell development increases progressively with age. IL-7Rα-mediated signals are required for the expression of many VH gene segments that are distal to DH-JH in the IgH locus and for the complete diversification of the BCR repertoire. Therefore, we hypothesized that B cells generated in the absence of IL-7 do not recognize a wide range of Ags because of a restricted BCR repertoire. Compared with adult wildtype mice, young wildtype mice and IL-7-deficient adult mice generated a significantly reduced Ab response to ViPS. Additionally, ViPS-binding B cells in adult wildtype mice predominantly used distal VH gene segments. Transgenic expression of either IL-7 or a BCR encoded by a distal VH gene segment permitted young mice to respond efficiently to bacterial polysaccharides. These results indicate that restricted VH gene usage early in life results in a paucity of Ag-specific B cell precursors, thus limiting antipolysaccharide responses.

PMID:
30006375
PMCID:
PMC6085875
[Available on 2019-08-15]
DOI:
10.4049/jimmunol.1800162

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