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  • Review Article
  • Published:

The double life of a B-1 cell: self-reactivity selects for protective effector functions

Nature Reviews Immunology volume 11, pages 34–46 (2011)Cite this article

Subjects

Key Points

  • B-1 cells are innate-like B cells that have features of both the adaptive and the innate immune systems.

  • The development of B-1 cells is distinct from that of conventional B-2 cells and leads to the establishment of a B cell subset with a B cell receptor (BCR) repertoire that is selected for self- and polyreactivity and that contains many evolutionarily 'useful' BCR specificities.

  • B-1 cells secrete these useful BCR specificities in the steady state as natural IgM (and IgA) antibodies, in the absence of antigenic stimulation.

  • B-1 cells do not respond readily to BCR-mediated stimulation by extensive clonal expansion, possibly owing to the expression of inhibitory co-receptors. However, they respond rapidly and vigorously to non-specific inflammatory and pathogen-associated stimuli, by migrating from the body cavities to secondary lymphoid tissues, where they undergo rapid differentiation to antibody-secreting cells.

  • Owing in part to their BCR repertoire and their particular response patterns, B-1 cells and the antibodies they secrete function as important regulators of homeostasis. B-1 cells can engulf and clear dead apoptotic cells, produce anti-inflammatory cytokines such as interleukin-10 and secrete IgA in the intestinal mucosa, thereby regulating the local microbiota.

  • B-1 cells are well described in mice, but not in humans. However, humans do generate natural polyreactive antibodies, and candidate functional human homologues of mouse B-1 cells are beginning to emerge.

Abstract

During their development, B and T cells with self-reactive antigen receptors are generally deleted from the repertoire to avoid autoimmune diseases. Paradoxically, innate-like B-1 cells in mice are positively selected for self-reactivity and form a pool of long-lived, self-renewing B cells that produce most of the circulating natural IgM antibodies. This Review provides an overview of the developmental processes that shape the B-1 cell pool in mice, outlines the functions of B-1 cells in both the steady state and during host defence, and discusses possible functional B-1 cell homologues that exist in humans.

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Figure 1: Mature splenic B cell subsets.
Figure 2: B-1 cell development in the steady state and after B-1 cell ablation.
Figure 3: Immune functions of B-1 cells.

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Acknowledgements

I would like to thank the current and previous members of my laboratory for their dedicated work allowing me to ponder and write about B-1 cells, and Lee and Len Herzenberg for their generosity and the tremendous opportunities they afforded me while I worked in their laboratory. I apologize to my colleagues whose work I could not adequately cite owing to space constraints. Current work relevant to this Review was supported by grants from the US National Institutes of Health/National Institute of Allergy and Infectious Diseases (AI051354 and AI073911).

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    Nicole Baumgarth

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Glossary

Natural antibodies

Antibodies found in individuals who have not had any previous known exposure to the antigens recognized by the antibodies.

T cell-independent antigens

Antigens that directly activate B cells.

Follicular B cells

Recirculating, mature B cells that continuously develop from precursors in the bone marrow and populate the follicles of the spleen and lymph nodes.

Marginal zone B cell

A type of mature B cell that is enriched in the marginal zone of the spleen. These cells recognize antigen through semi-invariant receptors, which stimulates their rapid differentiation to antibody-secreting cells. They are thought to be important for host defence against circulating blood-borne pathogens.

NZB/NZW F1 mice

The F1 generation of the cross between New Zealand black (NZB) mice and New Zealand white (NZW) mice. NZB/NZW F1 mice have a disease that closely resembles the human disease systemic lupus erythematosus.

Splanchnopleura region

An embryonic tissue in developing mice and birds that functions as an important site of primitive haematopoiesis

Terminal deoxynucleotidyl transferase (TdT)

An enzyme expressed during lymphocyte development that inserts nucleotides into the variable regions of T cell receptor and immunoglobulin genes, to create junctional diversity.

Negative selection

The process by which developing lymphocytes expressing potentially autoreactive antigen-specific receptors are induced to undergo apoptosis.

Omentum

A large fold of peritoneum between the stomach and abdomen that contains lymphoid aggregates known as 'milky spots'.

Coelomic cavities

Pleural and peritoneal body cavities, which are surrounded by a thin layer of serosa that contains the internal organs.

Follicular dendritic cells

Specialized non-haematopoietic stromal cells that reside in the lymphoid follicles and germinal centres. These cells have long dendrites and carry intact antigen on their surface. They are crucial for the optimal selection of B cells that produce antigen-binding antibody.

Class-switch recombination

This process alters the immunoglobulin heavy chain constant region (CH) gene that will be expressed by a B cell from the Cμ gene to one of the other CH genes. This results in a switch of immunoglobulin isotype from IgM/IgD to IgG, IgA or IgE, without altering antigen specificity.

Delayed-type hypersensitivity (DTH) response

A cellular immune response to antigen that develops over 24–72 hours with the infiltration of T cells and monocytes, and depends on the production of T helper 1 cell-specific cytokines.

Hapten

A molecule that can bind the B cell receptor but cannot by itself elicit an immune response. Antibodies that are specific for a hapten can be generated when the hapten is chemically linked to a protein carrier that can elicit a T cell response.

Recombination-activating gene 1 (Rag1)−/− mice

Recombination-activating genes (Rag1 and Rag2) are expressed in developing lymphocytes. Mice that are deficient for either of these genes fail to produce B or T cells owing to a developmental block in the gene rearrangement that is necessary for antigen receptor expression.

Common variable immunodeficiency

The most common symptomatic primary antibody deficiency, characterized by decreased levels of serum immunoglobulin, and a low or normal number of B cells. Most patients suffer from recurrent infections, mainly of the respiratory and gastrointestinal tracts. The incidence of malignancies, such as gastric carcinoma or lymphoma, is also increased in these patients.

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Baumgarth, N. The double life of a B-1 cell: self-reactivity selects for protective effector functions. Nat Rev Immunol 11, 34–46 (2011). https://doi.org/10.1038/nri2901

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