Receptor/ligand interactions in stromal microenvironments play important roles in the localization, development and survival of normal antibody-secreting plasma cells. The goal of the current study was to determine the impact of blocking CXCR4/CXCL12 interactions with plerixafor on the homeostasis of PCs in vivo. BALB/c mice were treated with plerixafor (up to 1 mg/kg x 10d). Blockade of CXCR4/CXCL12 mobilized a subpopulaton of splenic plasma cells into the peripheral blood. Bone marrow PCs did not appear to be mobilized by plerixafor. Total plasma cell numbers in the spleen and bone marrow remained constant, however, some plasma cells in both compartments appear to have been depleted and replaced by new ones. Splenic plasma cells from plerixafor-treated mice were more likely to undergo apoptosis soon after isolation suggesting subtle effects on the viability of these cells. However, blocking CXCR4/CXCL12 interactions did not enhance the depleting effects of the proteasome inhibitor, bortezomib. We conclude that CXCR4/CXCL12 interactions are important for the retention and longevity of a subpopulation of plasma cells in the spleen, but this interaction has minimal effect on plasma cells in the marrow. These data suggest that the use of plerixafor for the mobilization of hematopoietic stem cells should have minimal impact on antibody production of donors.

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