Date of Graduation

1988

Document Type

Dissertation/Thesis

Abstract

We have addressed the regulation of B lymphocyte formation by bone marrow stromal cells. Stromal cells appear to produce a regulatory factor which acts at the pre-B cell stage to induce the expression of immunoglobulin light chains and surface immunoglobulin. Bone marrow stromal cell conditioned medium was found to contain this factor and the active component was partially purified by HPLC. This stromal cell derived factor had a molecular weight between 16,000 and 20,000, was specifically neutralized by anti-IL-4 monoclonal antibody, 11B11, and enhanced the proliferation of anti-{dollar}\\mu{dollar} stimulated B cells. We also found that recombinant IL-4 induced B cell formation in culture. In our studies, IL-1 had no direct effect on pre-B cell maturation, however, IL-1 was found to stimulate the production of IL-4 by both heterogeneous bone marrow stromal cells and a cloned stromal cell line, SCL-160. These effects of IL-1 on factor production by stromal cells were duplicated by the addition of marrow-derived macrophages to SCL-160 cells. We conclude that stromal cell derived IL-4 is a physiologic stimulator for B cell generation. In addition, macrophages appear to play a role in B cell formation by regulating the production of IL-4 by stromal cells via the secretion of IL-1. Environmental exposure to benzene results in both myelotoxicity and immunotoxicity. We have studied the effect of the benzene metabolite, hydroquinone (HQ), on bone marrow B-lymphopoiesis. One hour exposure of marrow cells to HQ reduced the numbers of B cells generated in culture as the numbers of small pre-B cells were elevated when compared with control cultures. These results suggest that exposure to HQ inhibits B cell production by preventing the maturation of pre-B cells. Data presented in this dissertation demonstrate that HQ interrupts B-lymphopoiesis by indirectly altering IL-4 production by heterogeneous stromal cells. Our studies suggest that HQ inhibits macrophage production of IL-1, a potent inducer of IL-4 production by fibroblastic stromal cells. This interruption of IL-1 release from macrophages mediates the observed effect on B lineage cells via its effect on stromal cells necessary for B cell formation.

Download

Share

COinS