The B-cell receptor plays a positive role in the maturation and continued recirculation of peripheral B cells. Mice that lack the tyrosine kinase Syk, which is involved in signaling from the B-cell receptor (see Section 7-20), have immature B cells but fail to develop mature B cells. Thus, a Syk-transduced signal may be required for final B-cell maturation or for the survival of mature B cells. Furthermore, continuous expression of the B-cell receptor is required for B-cell survival, as is evident from the loss of all B cells in mice whose BCR is conditionally deleted specifically in mature B cells. Although each B-cell receptor has a unique specificity, antigen-specific interactions may not induce the signals used for final B-cell maturation and survival; the receptor could, for example, be responsible for ‘tonic’ signaling, in which a weak but important signal is generated by the assembly of the receptor complex and infrequently triggers some or all of the downstream signaling events.
8-9 B-1 B cells are an innate lymphocyte subset that arises early in development.
Thus far, this chapter has focused on the development of the majority populations of B cells that reside in secondary lymphoid organs, such as follicular (B-2) B cells and marginal zone B cells. These two populations comprise the B-cell arm of the adaptive immune response. A third important subset of B cells, called B-1 B cells, is part of the innate immune system. These cells are present only in low numbers in secondary lymphoid organs, and are found in large numbers in the peritoneal and pleural cavities instead. B-1 B cells are the major source of ‘natural’ antibodies, which are constitutively produced circulating antibodies that are secreted by these B cells prior to any infections. Most antibodies made by B-1 B cells recognize capsular polysaccharide antigens, and B-1 B cells are important in controlling infections of pathogenic viruses and bacteria.
One important feature of B-1 B cells is that they can produce antibodies of the IgM class without ‘help’ from T cells. Although this response can be enhanced by T-cell cooperation, the antibodies first appear within 48 hours of exposure to antigen, when T cells cannot be involved. The lack of an antigen-specific interaction with helper T cells might explain why immunological memory is not generated as a result of B-1 cell responses: repeated exposures to the same antigen elicit similar, or decreased, responses with each exposure. While the precise functions of B-1 B cells are still not clear, mice deficient in B-1 cells are more susceptible to infection with Streptococcus pneumoniae because they fail to produce an anti-phosphocholine antibody that provides protection against this bacterium. Since a significant fraction of the B-1 cells can make antibodies of this specificity, and because no antigen-specific T-cell help is required, a potent response can be produced early in infection with this pathogen. Whether human B-1 cells have the same role is not certain.