The control of B lymphocyte production in bone marrow is of central importance in maintaining a supply of new B cells for primary humoral immune responses throughout life, while its perturbation may underlie states of immunodeficiency, neoplasia and autoimmunity. Molecules expressed by developing B cells and stromal cells within bone marrow, as well as systemic factors, may all play key roles in regulating proliferation and survival of precursor B cells in bone marrow. Candidate regulatory molecules investigated in the present work include surrogate light chains (SL) of immunoglobulin (Ig) expressed intracellularly by precursor B cells before and during the synthesis of CI heavy (H) chains of IgM, and interleukin (IL)-1, a systemic pleiotropic macrophage-derived factor. In vivo administration of radiolabeled mAbs specific for SL and IL-1 receptors type I and type II revealed that both SL and IL-1 receptors are normally expressed in bone marrow, displayed on the surface of lymphoid precursors and stromal cells, respectively. Ex vivo analysis of the DNA content of SL/$ mu$H$ sp+$ pre-B cells revealed a low incidence of apoptosis. Systemic administration of rIL-1 followed by analysis of precursor B cell dynamics using double immunofluorescence labeling and stathmokinetic techniques revealed that systemic IL-1 can either stimulate or depress B lymphopoiesis in a dose-dependent manner. Stimulation of cytoplasmic (c) $ mu sp+$ pre-B cell proliferation following activation of systemic macrophages by injecting sheep red blood cells (SRBC) is partially abrogated by rIL-1ra. Bone marrow IL-1 receptors, assayed by binding of radiolabeled anti-IL-1R monoclonal antibodies to plasma membrane fractions, undergo changes in levels of expression following SRBC administration. The work supports the hypotheses that surface SL is involved in the positive selection of precursor B cells with productively-rearranged $ mu$ chain genes, and suggests that the elevated proliferative level o
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.42027 |
| Date | January 1996 |
| Creators | Fauteux, Lucy J. (Lucy Jacinthe) |
| Contributors | Osmond, Dennis G. (advisor) |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Doctor of Philosophy (Department of Anatomy and Cell Biology.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 001548758, proquestno: NQ29932, Theses scanned by UMI/ProQuest. |
Page generated in 0.0019 seconds