Date of Award


Degree Type


Degree Name

Doctor of Philosophy


The bone marrow is a primary lymphoid organ whose main function is to provide a continuous source of hematopoietic cells to the peripheral immune system. This study was undertaken to elucidate the roles of bone marrow cells and their mediators in immunoregulation.;Fractionation of bone marrow cells resolved two distinct immunoregulatory activities. A population of bone marrow cells of the phenotype HNK-1{dollar}\sp{lcub}+{rcub}{dollar} (human natural killer cell antigen, CD57), SSEA-1{dollar}\sp{lcub}+{rcub}{dollar} (stage specific embryonic antigen) and OKM1{dollar}\sp{lcub}+{rcub}{dollar} (human monocyte antigen, CD11B) was found to be highly suppressive for primary antibody responses. Conversely, a lymphocyte enriched bone marrow cells fraction could enhance the same antibody response. Neither population expressed surface markers for mature T nor B cells. Noteworthy was the finding that bone marrow depleted of natural suppressor cells was capable of mounting a primary antibody response. In addition, the two bone marrow cell populations acted antagonistically in the regulation of IgM antibody responses.;Both activities are mediated by soluble factors. Bone marrow Derived Suppressor Factor (BDSF) is a phospholipid that is synthesized de novo by HNK-1{dollar}\sp{lcub}+{rcub}{dollar} bone marrow cells during a 24 hour culture. BDSF appears to mediate its suppressive effects by inhibiting interleukin-1 synthesis. On the other hand, Bone marrow Derived Enhancing Factor (BDEF) is a glycoprotein of MW 60,000 daltons and has the additional property of being directly mitogenic for both bone marrow cells and thymocytes. Both molecules act during the inductive phase of the generation of antibody responses and their action is not restricted by major histocompatibility antigens.;The fact that both activities are constitutively present within the bone marrow, in conjunction with their antagonistic action, make them ideally situated mediators to regulate bone marrow immunoglobulin levels. Furthermore, their potential effects on bone marrow stem cells suggest that the two activities contribute to the maintenance of bone marrow homeostasis.



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