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J Immunol. 2021 Jul 01;207(1):77-89. doi: 10.4049/jimmunol.2001173. Epub 2021 Jun 16.

CD40L-Stimulated B Lymphocytes Are Polarized toward APC Functions after Exposure to IL-4 and IL-21.

Journal of immunology (Baltimore, Md. : 1950)

David Possamaï, Gabriel Pagé, Rébecca Panès, Étienne Gagnon, Réjean Lapointe

Affiliations

  1. Axe Cancer, Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Montréal, Québec, Canada.
  2. Faculté de Médecine, Département de Médecine, Université de Montréal, Montréal, Québec, Canada.
  3. Axe de Recherche en Immunobiologie du Cancer, Institut de Recherche en Immunologie et Cancérologie, Montréal, Québec, Canada; and.
  4. Faculté de Médecine, Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montréal, Québec, Canada.
  5. Axe Cancer, Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Montréal, Québec, Canada; [email protected].

PMID: 34135061 DOI: 10.4049/jimmunol.2001173

Abstract

B lymphocytes have multiple functions central to humoral immunity, including Ag presentation to T cells, cytokine secretion, and differentiation into Ab-secreting plasma cells. In vitro expansion of human B cells by continuous IL-4 stimulation and engagement of their CD40 receptor by CD40L has allowed the use of these IL-4-CD40-B cells in research for the induction of Ag-specific T cell immune responses. However, in vivo, follicular helper T cells also influence B cell activity through the secretion of IL-21. The impact of both cytokines on multiple B cell functions is not clearly defined. To further understand these cytokines in CD40-B cell biology, we stimulated CD40-B cells with IL-4 or IL-21 or both (Combo) and characterized the proliferation, subsets, and functions of these cells. We demonstrate that IL-21- and Combo-CD40-B cells are highly proliferative cells that can be rapidly expanded to high numbers. We show that IL-21-CD40-B cells polarize to Ab-secreting plasma cells, whereas IL-4- and Combo-CD40-B cells are mostly activated mature B cells that express molecules associated with favorable APC functions. We further demonstrate that both IL-4- and Combo-CD40-B cells are efficient in promoting T cell activation and proliferation compared with IL-21-CD40-B cells. Thus, our study provides a better appreciation of CD40-B cell plasticity and biology. In addition, the stimulation of B cells with CD40L, IL-4, and IL-21 allows for the fast generation of high numbers of efficient APC, therefore providing a prospective tool for research and clinical applications such as cancer immunotherapy.

Copyright © 2021 by The American Association of Immunologists, Inc.

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