Interleukin-7-dependent B lymphocytes are required for the anti-pneumococcal polysaccharide response and protective immunity to Streptococcus pneumoniae

Authors

Gregory S. Dickinson, PhD, Thomas Jefferson UniversityFollow
Raja Vuyyuru, Thomas Jefferson UniversityFollow
Timothy L. Manser, PhD, Thomas Jefferson UniversityFollow
John F. Kerney, University of Alabama - Birmingham
Kishore Alugupalli, PhD, Thomas Jefferson UniversityFollow

Document Type

Poster

Publication Date

4-2014

Abstract

Unlike human adults or adult mice, young children or young mice respond poorly to pneumococcal polysaccharides (PPS). In mice, B1b lymphocytes are the major responders to a variety of bacterial polysaccharides including PPS. Despite having B1b cells, young mice are severely impaired in responding to PPS, suggesting that B cells in the young are distinct from those in adults. Since B lymphopoeisis early in life is largely Interleukin-7 (IL-7)-independent, while in adults it is IL-7-dependent, we hypothesize that B cells developed in the presence of IL-7 are required for generating anti-PPS antibody responses. In support of this, we found that despite having B1b cells, young wildtype and adult mice deficient either in IL-7 or IL-7Rα are severely impaired in responding to Pneumovax^®23 vaccine, and do not survive pneumococcal challenge. Furthermore, we found that transgenic expression of IL-7 promotes the anti-PPS response in young and confers protective immunity to young mice. To translate these findings to human infants we have utilized neonatal NOD/SCID/gc^null mice engrafted with human umbilical cord blood CD34⁺ hematopoietic stem cells to create a "Human Immune System" mouse (HISmouse) model. We have found that these HISmice generate several B cell subsets including B1 (CD19⁺CD20⁺CD27⁺CD43⁺CD70^-CD69^-) and the majority of them exhibit an immature phenotype. Moreover, just as young children, HISmice responded poorly to PPS. IL-7 is produced mainly by non-hematopoietic stromal cells, and unlike the human IL-7, the murine IL-7 is poor stimulator of human B lymphocyte development. Although our data indicate that IL-7-dependent B cells are crucial for generating anti-polysaccharide response, we also found that enforced expression of a polysaccharide (a1,3, dextran)-specific B cell antigen receptor heavy chain (V_H J558) in mice can overcome the lack of anti-polysaccharide antibody responses in young mice even in the absence of an IL-7-dependent B lymphopoiesis.

Recommended Citation

Dickinson, PhD, Gregory S.; Vuyyuru, Raja; Manser, PhD, Timothy L.; Kerney, John F.; and Alugupalli, PhD, Kishore, "Interleukin-7-dependent B lymphocytes are required for the anti-pneumococcal polysaccharide response and protective immunity to Streptococcus pneumoniae" (2014). Department of Microbiology and Immunology Faculty Papers. Paper 59.
https://jdc.jefferson.edu/mifp/59