The effect of BLyS neutralization on primary B cell compartments and responses (B31)

Abstract B lymphocyte stimulator (BLyS) controls the proportion of transitional B cells completing differentiation and the longevity of most primary B cells. These key roles in B cell selection, survival and homeostasis make BLyS and its receptors attractive candidates for targeted B cell therapeutics. Here we have used a neutralizing hamster anti-mouse BLyS antibody to assess how BLyS depletion influences developing and primary B cell subsets, as well as how this treatment impacts primary TD and TI immune responses. Mice treated with 10F4 show rapid and substantial reductions in the transitional, follicular, and marginal zone pools which persist for ~40 days. In contrast, the only bone marrow subset affected is the mature recirculating B cell fraction. Interestingly, splenic B1 cells, but not peritoneal B1 cells, are reduced as well. Following the recovery of serum BLyS levels, peripheral reconstitution occurs gradually, such that normal B cell numbers return by day 70–80. Mice challenged with T-dependent or T-independent antigen at day 30 post-treatment with anti-BLyS mount attenuated humoral responses compared with untreated mice. Together, our results show that BLyS neutralization ablates most primary B cells but spares B lineage progenitors; and indicate that these populations, as well as BLyS per se, may be required for unabridged primary immune responses.