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  • Review Article
  • Published:

Fetal B-cell lymphopoiesis and the emergence of B-1-cell potential

Nature Reviews Immunology volume 7, pages 213–219 (2007)Cite this article

Key Points

  • Two populations of B cells, B-1 cells and B-2 cells, have been described in mice. B-2 cells are produced in the bone marrow during postnatal life. Most B cells in peripheral lymphoid tissues are B-2 cells and they are generally involved in adaptive immune responses. B-1 cells are a minor population of B cells; they constitute a high proportion of B cells in serous cavities and are generally effectors of innate immune responses.

  • B-cell development initiates during embryogenesis. Cells with B-cell potential are present in multiple intra-embryonic and extra-embryonic tissues. However, B-cell potential seems to be initially associated with the intra-embryonic para-aortic splanchnopleura.

  • There is strong circumstantial evidence that the potential of haematopoietic precursors to produce B-1 cells arises before B-2-cell potential.

  • There has been considerable debate regarding the origin of B-1 cells. The selection model proposes that they are generated from surface-IgM-expressing B-2 cells in response to specific types of antigen. The lineage model proposes that B-1 and B-2 cells are distinct lineages with separate progenitors. The recent description of a population of CD19+CD45−/low cells that can only produce B-1 cells provides support for the lineage model.

  • Progenitors with B-1-cell potential are preferentially produced in the embryo and B-2-cell progenitors arise late during embryogenesis and are preferentially produced in the adult. It is not clear why this is the case, although differences in the fetal and adult environment may be a factor.

  • Much needs to be learned about human B-cell development. There is circumstantial evidence that B-1 cells are present in humans, but further investigation of this issue is needed.

Abstract

Most B cells in peripheral lymphoid tissues are produced in adult bone marrow and are referred to as B-2 cells. A minor B-cell population, known as the B-1-cell population, that is mainly involved in innate immune responses has been identified in mice. In contrast to B-2 cells, B-1-cell progenitors are produced most efficiently during fetal life. This Review focuses on the emergence of B-1-cell potential during embryogenesis, summarizes recent advances in the delineation of a fetal B-1-cell-specified progenitor, and discusses the possibility that distinct fetal and adult B-cell developmental programmes might be operative in humans.

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Figure 1: Emergence of B-cell precursor potential during embryogenesis.
Figure 2: B-2-cell development in adult bone marrow.
Figure 3: Models of fetal B-cell development.

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Acknowledgements

We thank H. Mikkola for her review of the manuscript. The original work from our laboratory reported herein was supported by the National Institutes of Health, USA.

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  1. Jonsson Comprehensive Cancer Center and the Department of Pathology and Laboratory Medicine, Hematopoietic Malignancies Program, David Geffen School of Medicine at UCLA, 10833 Le Conte Avenue, Los Angeles, 90095, California, USA

    Kenneth Dorshkind & Encarnacion Montecino-Rodriguez

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  1. Kenneth Dorshkind
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Correspondence to Kenneth Dorshkind.

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Glossary

Marginal-zone B cell

A sessile, mature B-cell subset that co-localizes to the spleen marginal zone, which is located at the border of the white pulp.

Follicular B cell

A re-circulating, mature B-cell subset that populates the follicles of the spleen and lymph nodes.

CD45R

A member of the CD45 leukocyte common antigen family that includes glycoproteins of multiple sizes generated by alternative splicing of the CD45 mRNA and subsequent glycosylation of the CD45 protein. Two 220 kDa molecular weight isoforms of CD45, CD45R and CD45RA, have been described and are distinguished by distinct patterns of glycosylation. Although the term B220 has been used interchangeably to describe both molecules, the antibodies used to identify the B-1-cell progenitors31 referred to in this Review specifically recognize the CD45R determinant.

B-cell receptor

The cell-surface receptor on mature B cells, composed of the transmembrane immunoglobulin molecule associated with the Igα and Igβ chains.

Para-aortic splanchnopleura

(PAS). The embryonic tissue formed by the association of the mesoderm and endoderm. It is located on either side of the aorta. The AGM region subsequently develops from the PAS.

Aorta–gonad–mesonephros

(AGM). An embryonic site in which the development of definitive haematopoietic stem cells (HSCs) occurs. It comprises the aorta, and developing reproductive and excretory (mesonephros) systems. In this haematogenic site, HSCs are concentrated in the aorta region.

γδ T cells

T cells that express heterodimers consisting of the γ- and δ-chains of the T-cell receptor. They are mainly present in the intestinal epithelium as intraepithelial lymphocytes (IELs). Although the exact function of γδ T cells (or IELs) is still unknown, it has been proposed that mucosal γδ T cells are involved in the innate immune responses of the mucosal immune system.

Omentum

A generic term that refers to folds of the peritoneum. The lesser omentum consists of two layers of peritoneum and passes between the liver and the stomach. The greater omentum consists of four layers of peritoneum that extend below the stomach.

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Dorshkind, K., Montecino-Rodriguez, E. Fetal B-cell lymphopoiesis and the emergence of B-1-cell potential. Nat Rev Immunol 7, 213–219 (2007). https://doi.org/10.1038/nri2019

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