B Cell Precursors in Bone Marrow: In Vivo Proliferation, Localization, Stimulation by Activated Macrophages and Implications for Oncogenesis

Abstract

Precursor cells in mammalian bone marrow continuously give rise to virgin B lymphocytes by undergoing a series of genetic, mitotic and selection events (Osmond 1985, 1986, Osmond & Park 1987). During the differentiation of individual precursor cells the B cell antigen-binding specificities are determined by the formation of functional Ig variable (V) region genes from a combination of gene segments (Tonegawa 1983). The enzyme terminal deoxynucleotidyl transferase (TdT) can insert additional nucleotides during rearrangement of the heavy (H) chain gene, contributing to B cell diversity (Yancopoulos et al 1984, Kunkel et al 1986). Thereafter, however, the mitotic activity of the precursor B cells largely dictates the ultimate output of B cell clones, especially with respect to clone size (the number of B cells having a given antigen-binding specificity) and the number of different clones produced per unit time. This process may be modified by cell loss. The combined genetic and mitotic activities of early precursor B cells make them susceptible to genetic errors which may result in cell death. Other non-lethal aberrations could predispose to gene dysregul-ation and oncogenesis (Greaves 1986, Lenoir & Bornkum 1987, Harris et al 1988).