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Integrating B cell homeostasis and selection with BLyS

100%

Smith S. H., Cancro M. P.

Archivum Immunologiae et Therapiae Experimentalis

2003

vol. 51

issue 4

209-218

The mechanisms that maintain a pool of B cells that is adequately diverse yet devoid of pathogenic autoreactivity remain poorly understood. B cells complete maturation after migrating to the periphery, where they transit several intermediate developmental stages prior to recruitment into the long-lived primary pool. Since B lineage commitment is not coupled to peripheral B cell numbers and most mature peripheral B cells are quiescent, the sizes of mature peripheral compartments are primarily determined by the proportion of immature B cells that survive transit through later developmental stages, coupled with the longevity of mature B cells themselves. Compelling evidence indicates that the B cell antigen receptor (BcR) plays an essential role in all of these processes, but further findings indicate a similar role for the recently described tumor necrosis factor family member, B lymphocyte stimulator (BLyS). Signaling through the BLyS receptor, Bcmd/BR3, controls B cell numbers in two ways: by varying the proportion of cells that complete transitional B cell development, and by serving as the primary determinant of mature B cell longevity. The striking congruence of BcR- and BLyS-mediated effects on B cell selection and survival suggests these pathways may be related. The recent discovery that BcR signaling is selectively coupled to Bcmd/BR3 expression links BcR- and BLyS-mediated activities in transitional and mature B cells, suggesting specificity-based selection and survival may be mechanistically similar processes.

Manipulating B cell homeostasis: a key component in the advancement of targeted strategies

71%

Treml L. S., Quinn I. W. J., Treml J. M., Scholz J. L., Cancro M. P.

Archivum Immunologiae et Therapiae Experimentalis

2008

vol. 56

issue 3

153-164

Understanding the homeostatic mechanisms governing lymphocyte pools achieves critical importance as lymphocyte-targeted therapies expand in use and scope. The primacy of B lymphocyte stimulator (BLyS) family ligands and receptors in governing B lymphocyte homeostasis has become increasingly clear in recent years, affording insight into novel opportunities and potential pitfalls for targeted B cell therapeutics. Interclonal competition for BLyS-BR3 interactions determines the size of na?ve B cell pools and can regulate the stringency of selection applied as cells complete maturation. Thus one of the predicted consequences of ablative therapies targeting primary pools is relaxed negative selection. This suggests that BLyS levels and B cell reconstitution rates may serve useful prognostic roles and that BLyS itself might be targeted to circumvent relapse. Alternatively, manipulations that allow rare, minimally autoreactive specificities to survive and mature may lead to opportunities in cases where antibody-based vaccine development has heretofore been unsuccessful. BLyS family ligands and receptors also play a role in activated and memory B cell pools, suggesting they might likewise be targeted to promote or delete particular antigen-experienced subpopulations in a similar way.

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2 Archivum Immunologiae et Therapiae Experimentalis

1 2008

1 2003

2 Cancro M. P.

1 Quinn I. W. J.

1 Scholz J. L.

1 Smith S. H.

1 Treml J. M.

1 Treml L. S.

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Integrating B cell homeostasis and selection with BLyS

Manipulating B cell homeostasis: a key component in the advancement of targeted strategies