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Microbes Infect. 2019 Apr - May;21(3-4):176-183. doi: 10.1016/j.micinf.2018.12.002. Epub 2018 Dec 21.

Cognate T and B cell interaction and association of follicular helper T cells with B cell responses in Vibrio cholerae O1 infected Bangladeshi adults.

Author information

1
Infectious Diseases Division, International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka, Bangladesh.
2
Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA, USA; Department of Pediatrics, Harvard Medical School, Boston, MA, USA.
3
Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA, USA; Department of Medicine, Harvard Medical School, Boston, MA, USA; Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
4
Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA, USA; Department of Medicine, Harvard Medical School, Boston, MA, USA; Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA, USA.
5
Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA, USA; Department of Medicine, Harvard Medical School, Boston, MA, USA.
6
Infectious Diseases Division, International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka, Bangladesh. Electronic address: fqadri@icddrb.org.

Abstract

Vibrio cholerae O1 can cause life threatening diarrheal disease if left untreated. T cells can play critical roles in inducing B cell mediated immunity. As the mechanism of T cell dependent B cell maturation is not well established, we hypothesized that a specific population of T (follicular helper T, Tfh) cells, are involved in B cell maturation following cholera. We found flowcytometrically that V. cholerae infection induces significant increases in circulating Tfh cells expressing B cell maturation associated protein CD40L early in disease. The increased Tfh cells expressing CD40L recognize cholera toxin most prominently, with lessened responses to V. cholerae membrane preparation (MP) and V. cholerae cytolysin (VCC). We further showed that early induction of Tfh cells and CD40L was associated with later memory B cell responses to same antigens. Lastly, we demonstrated in vitro that Tfh cells isolated after cholera can stimulate class switching of co-cultured, isolated B cells from patients with cholera, leading to production of the more durable IgG antibody isotype colorimetrically. These studies were conducted on circulating Tfh cells; future studies will be directed at examining role of Tfh cells during cholera directly in gut mucosa of biopsied samples, at the single cell level if feasible.

KEYWORDS:

B cells; CD40L; CXCR5; Cholera; Follicular helper T cells

PMID:
30580014
PMCID:
PMC6588510
DOI:
10.1016/j.micinf.2018.12.002
[Indexed for MEDLINE]
Free PMC Article

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