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Memory B cells

Nature Reviews Immunology volume 24, pages 5–17 (2024)Cite this article

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Abstract

Recent advances in studies of immune memory in mice and humans have reinforced the concept that memory B cells play a critical role in protection against repeated infections, particularly from variant viruses. Hence, insights into the development of high-quality memory B cells that can generate broadly neutralizing antibodies that bind such variants are key for successful vaccine development. Here, we review the cellular and molecular mechanisms by which memory B cells are generated and how these processes shape the antibody diversity and breadth of memory B cells. Then, we discuss the mechanisms of memory B cell reactivation in the context of established immune memory; the contribution of antibody feedback to this process has now begun to be reappreciated.

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Fig. 1: GC dynamics and memory B cell selection.
Fig. 2: Generation of GC-independent and GC-dependent memory B cells.
Fig. 3: Memory B cell generation from GCs.
Fig. 4: Memory B cell reactivation.

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Acknowledgements

The authors thank P. D. Burrows for critical reading of the manuscript. This work was supported, in part, by Japan Society for the Promotion of Science KAKENHI (JP21H02749 to T.I., JP22H00450 to T.K.), the Mochida Memorial Foundation for Medical and Pharmaceutical Research (to T.I.) and the Chemo-Sero-Therapeutic Research Institute (to T.I.).

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Authors and Affiliations

  1. Laboratory of Lymphocyte Differentiation, WPI Immunology Frontier Research Center, Osaka University, Osaka, Japan

    Takeshi Inoue & Tomohiro Kurosaki

  2. Graduate School of Frontier Biosciences, Osaka University, Osaka, Japan

    Tomohiro Kurosaki

  3. Center for Infectious Disease Education and Research, Osaka University, Osaka, Japan

    Tomohiro Kurosaki

  4. Laboratory for Lymphocyte Differentiation, RIKEN Center for Integrative Medical Sciences (IMS), Kanagawa, Japan

    Tomohiro Kurosaki

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  1. Takeshi Inoue
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T.K. contributed to conceptualization of the article. All authors contributed to writing and editing of the manuscript.

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Correspondence to Tomohiro Kurosaki.

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Glossary

Affinity maturation

A process, as a result of somatic hypermutation (SHM) and B cell selection in the germinal centre (GC), by which B cells increase their affinity and avidity for the antigens.

Age-associated B cells

(ABCs). A subset of B cells expressing CD11c and the transcription factor T-bet, and lacking CD21 in mice. ABCs are shown to increase during both ageing and autoimmunity.

Antibody feedback

An immunological phenomenon in which antibodies can either enhance or suppress the antigen-specific B cell responses.

Atypical memory B cells

A subset of memory B cells expressing inhibitory molecules and lacking surface CD21 and CD27 in humans. Atypical memory B cells often develop in individuals with chronic infection or autoimmune disease, and are characterized by their reduced effector function.

B1 and B2 B cells

B cell populations that differ in development, tissue localization and function. B2 B cells are the major and conventional B cell population abundant in the spleen, lymph nodes and peripheral blood, which participate in the germinal centre (GC) reaction to produce high-affinity antibodies. B1 B cells are enriched in the peritoneal and pleural cavities, which recognize self-components and common bacterial antigens, and are the major source of natural IgM antibodies.

T follicular helper cells

(TFH cells). A subset of activated CD4+ T cells expressing the chemokine receptor CXCR5 and the transcription factor BCL-6. TFH cells provide help to B cells for activation, germinal centre (GC) formation and affinity maturation.

Somatic hypermutation

(SHM). A process by which B cells accumulate point mutations in their immunoglobulin genes, thus diversifying the specificity and affinity of their B cell receptors (BCRs) for the antigens.

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Inoue, T., Kurosaki, T. Memory B cells. Nat Rev Immunol 24, 5–17 (2024). https://doi.org/10.1038/s41577-023-00897-3

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