Title

The regulatory effects of Ly-1 B lymphocytes: Premalignant or transformed Ly-1 B lymphocytes down-regulate B cell development

Date of Award

1991

Availability

Article

Degree Name

Doctor of Philosophy (Ph.D.)

Department

Microbiology and Immunology

First Committee Member

Richard Riley, Committee Chair

Abstract

The Ly-1 B cell population is both phenotypically and functionally different from conventional B cells. Ly-1 B cell populations are found associated with autoimmune diseases and chronic lymphocytic leukemias in both mice and man. Furthermore, Ly-1 B cells have been shown to have regulatory properties that effect the growth and functions of both Ly-1$\sp{+}$ and conventional Ly-1$\sp{-}$ B cell populations. In this investigation, studies were performed to identify the effects of Ly-1 B cell populations on B lymphopoiesis both in vitro and in vivo. Transformed Ly-1 B cell lines secreted products which directly inhibited the growth of pre-B cells in response to IL-7 in vitro, but did not inhibit the pre-B to B cell transition. In addition, cytokines secreted by transformed Ly-1 B cell lines altered the capacity of bone marrow stromal cells to support pre-B cell growth. These effects of Ly-1 B cells appeared to correlate with their transformation since, in contrast, normal peritoneal Ly-1 B cells did not inhibit pre-B cell growth in vitro.The regulation of pre-B cell proliferation by Ly-1 B cells may be relevant in vivo under conditions where Ly-1 B cells are unusually expanded and/or are undergoing transformation. Age-related declines in pre-B cells were not due to a dysfunctional bone marrow stromal cell microenvironment, but correlated with expansions in Ly-1 B cell populations in both autoimmune mice (NZB and (NZB x NZW) F1) and senescent normal mice. In order to determine whether spontaneous development of transformed Ly-1 B cells actively suppresses B lymphopoiesis in vivo, premalignant NZB splenic B cells were adoptively transferred to normal recipients. The expansion of NZB-derived Ly-1 B cells and their presence in both recipient spleen and bone marrow correlated with reductions in both pre-B cell numbers and mitotic activity within the bone marrow. Together, these experiments demonstrated that Ly-1 B cells in the process of expansion, activation, and/or transformation are immunoregulatory and may participate in the down-regulation of B lymphopoiesis.

Keywords

Health Sciences, Immunology

Link to Full Text

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