BLyS inhibition eliminates primary B cells but leaves natural and acquired humoral immunity intact

doi:10.1073/pnas.0807841105

BLyS inhibition eliminates primary B cells but leaves natural and acquired humoral immunity intact

*Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6082;
^§Human Genome Sciences, Inc., 14200 Shady Grove Road, Rockville, MD 20850; and
Departments of ^¶Immunology and Laboratory Medicine and
^‡Dermatology, Yale University School of Medicine, New Haven, CT 06520-8035

Communicated by Michael Potter, National Institutes of Health, Bethesda, MD, August 8, 2008
↵^†J.L.S. and J.E.C. contributed equally to this work. (received for review March 13, 2008)

Abstract

We have used an inhibiting antibody to determine whether preimmune versus antigen-experienced B cells differ in their requisites for BLyS, a cytokine that controls differentiation and survival. Whereas in vivo BLyS inhibition profoundly reduced naïve B cell numbers and primary immune responses, it had a markedly smaller effect on memory B cells and long-lived plasma cells, as well as secondary immune responses. There was heterogeneity within the memory pools, because IgM-bearing memory cells were sensitive to BLyS depletion whereas IgG-bearing memory cells were not, although both were more resistant than naïve cells. There was also heterogeneity within B1 pools, as splenic but not peritoneal B1 cells were diminished by anti-BLyS treatment, yet the number of natural antibody-secreting cells remained constant. Together, these findings show that memory B cells and natural antibody-secreting cells are BLyS-independent and suggest that these pools can be separately manipulated.

Footnotes

^‖To whom correspondence should be addressed. E-mail: cancro{at}mail.med.upenn.edu
Author contributions: J.L.S., J.E.C., M.M.T., N.S., T.-S.M., M.J.S., and M.P.C. designed research; J.L.S., J.E.C., N.S., P.J.O., W.J.Q., R.G., J.P.M., Y.H.C., V.L., C.W., and M.P.C. performed research; T.-S.M. and M.J.S. contributed new reagents/analytic tools; J.L.S., J.E.C., M.M.T., N.S., P.J.O., W.J.Q., R.G., J.P.M., Y.H.C., V.L., C.W., M.J.S., and M.P.C. analyzed data; and J.L.S., J.E.C., M.M.T., M.J.S., and M.P.C. wrote the paper.
Conflict of interest statement: M.P.C. was supported in part by a sponsored research agreement between Human Genome Sciences, Inc., and the University of Pennsylvania.
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