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  • Review Article
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Antibody-independent functions of B cells: a focus on cytokines

Key Points

  • Through the production of cytokines, B cells influence multiple aspects of immunity. B cell-derived cytokines guide the development of lymphoid tissues, shape and promote effector and memory T cell responses and can also negatively regulate immune responses.

  • The roles of B cells in lymphoid organogenesis often depends on their production of lymphotoxin α1β2 (LTα1β2). B cells can drive tertiary lymphoid tissue formation independently of lymphoid tissue-inducer cells by producing LTα1β2.

  • Following tissue damage, B cells can produce cytokines that influence tissue regeneration and pathophysiology in non-immunological organs.

  • B cells can control the polarization of effector T cell responses and the formation of memory T cells through the provision of cytokines.

  • B cells can negatively regulate immune response by producing interleukin-10 (IL-10) and IL-35. Subsets of CD19+CD138hi 'regulatory plasma cells' are the major sources of these B cell-derived suppressive cytokines in vivo.

  • B cells from mice infected with helminth parasites can inhibit allergic inflammation through the production of IL-10.

Abstract

Cytokine production by B cells is important for multiple aspects of immunity. B cell-derived cytokines, including lymphotoxin, are essential for the ontogenesis, homeostasis and activation of secondary lymphoid organs, as well as for the development of tertiary lymphoid tissues at ectopic sites. Other B cell-derived cytokines, such as interleukin-6 (IL-6), interferon-γ and tumour necrosis factor, influence the development of effector and memory CD4+ T cell responses. Finally, B cells can regulate inflammatory immune responses, primarily through their provision of IL-10 and IL-35. This Review summarizes these various roles of cytokine-producing B cells in immunity and discusses the rational for targeting these cells in the clinic.

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Figure 1: Role of lymphotoxin α1β2-expressing B cells in lymphoid organ development and function.
Figure 2: Role of cytokine-producing B cells in the polarization of CD4+ T cells.
Figure 3: Regulatory functions of cytokine-producing B cells.

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Acknowledgements

The laboratory of S.F. is supported by grants from the Deutsche Forschungsgemeinschaft (SFB-650, TRR-130 and FI-1238/02), Hertie Stiftung, the ERA-NET Anti-bacterial Immune Regulation (ABIR) grant and an advanced grant from the Merieux Institute.

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Shen, P., Fillatreau, S. Antibody-independent functions of B cells: a focus on cytokines. Nat Rev Immunol 15, 441–451 (2015). https://doi.org/10.1038/nri3857

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