Review Article | Published:

Memory B cells

Nature Reviews Immunology volume 15, pages 149159 (2015) | Download Citation


The immune system can remember a previously experienced pathogen and can evoke an enhanced response to reinfection that depends on memory lymphocyte populations. Recent advances in tracking antigen-experienced memory B cells have revealed the existence of distinct classes of cells that have considerable functional differences. Some of these differences seem to be determined by the stimulation history during memory cell formation. To induce rapid recall antibody responses, the contributions of other types of cells, such as memory T follicular helper cells, have also now begun to be appreciated. In this Review, we discuss these and other recent advances in our understanding of memory B cells, focusing on the underlying mechanisms that are required for rapid and effective recall antibody responses.

Key points

  • Germinal centre-independent memory B cells are generated from CD38+GL7+ activated B cells. These memory B cells may maintain broad reactivity to the activating pathogen.

  • B1a and B1b cells can generate T cell-independent memory B cells.

  • IgG+ and IgM+ memory B cells have a distinct function. IgG+ memory B cells preferentially differentiate into plasma cells, whereas IgM+ memory B cells predominantly enter the germinal centre reaction.

  • Bona fide IgE+ memory B cells are not present or, if they exist, they are present only as a small population.

  • Stimulation history, rather than the unique properties of the IgG cytoplasmic tail, is essential for exerting the rapid responses of IgG+ memory B cells.

  • Memory T follicular helper cells support memory B cell responses. During this step, memory B cells are crucial antigen-presenting cells.

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The authors thank Y. Takahashi and P. D. Burrows for critical reading of the manuscript, and T. Inoue for sharing unpublished data. This work was supported in part by grants provided by the Ministry of Education, Culture, Sports, Science, and Technology in Japan (to W.I. and T.K.); Japan Science and Technology Agency, Core Research for Evolutional Science and Technology (CREST; to T.K.); Secom Science and Technology Foundation (to T.K.); and RIKEN Special Postdoctoral Researchers Program (to K.K.).

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Author notes

    • Kohei Kometani

    Present address: Department of Cellular and Molecular Immunology, Max Planck Institute of Immunobiology and Epigenetics, Freiburg 79108, Germany.


  1. Laboratory of Lymphocyte Differentiation, World Premier International Immunology Frontier Research Center and Graduate School of Frontier Biosciences, Osaka University, 3–1 Yamada-oka, Suita, Osaka 565–0871, Japan.

    • Tomohiro Kurosaki
    •  & Wataru Ise
  2. Laboratory for Lymphocyte Differentiation, RIKEN Center for Integrative Medical Sciences, Tsurumi-ku, Yokohama, Kanagawa 230–0045, Japan.

    • Tomohiro Kurosaki
    •  & Kohei Kometani


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Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Tomohiro Kurosaki.


Isotype switching

A switch recombination in DNA that encodes the constant region of the immunoglobulin heavy chain, from IgM to any of IgG, IgA or IgE. The recombination occurs in repetitive DNA sequences (switch regions) that are located upstream of each constant region gene.

Somatic hypermutation

A process in which point mutations are generated in the variable regions of immunoglobulin genes, thus creating a more specific repertoire when combined with selection. Some mutations might increase the affinity of the B cell receptor (BCR) for the specific antigen, but others might lead to a loss of antigen recognition by the BCR or to the generation of a self-reactive receptor.

T follicular helper cells

(TFH cells). A distinct subset of antigen-activated CD4+ T cells expressing CXC-chemokine receptor 5 and B cell lymphoma 6. TFH cells are essential for germinal centre formation and regulate the activation and function of germinal centre B cells.

B2 cells

The major and conventional B cell population in humans and mice. Marginal zone and follicular B cells belong to the B2 cell lineage and arise from bone marrow precursor cells.

B1 cells

A self-renewing subset of mature B cells that predominates in the peritoneal and pleural cavities. B1 cells recognize self components, as well as common bacterial antigens, and are primarily responsible for the production of natural serum IgM.

Fibroblastic reticular cells

(FRCs). The most abundant population of non-haematopoietic or stromal cells in T cell-rich areas of secondary lymphoid organs. FRCs facilitate interactions between T cells and dendritic cells, through the expression of cytokines and chemokines, such as interleukin-7, CC-chemokine ligand 19 (CCL19) and CCL21.


A term that was initially used to describe a state of T cell dysfunction that arises during many chronic infections and in cancer, and is typified by the increased expression of programmed cell death protein 1.

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