Immunoglobulin gene rearrangements in pre-B cells.

Abstract

Although the existence of antibodies and their induction by antigen had been shown by von Behring and Kitasato in the 1890s, the cellular origin of antibodies remained controversial right up to the late 1940s, when it was determined that plasma cells contained large amounts of immunoglobulin (Ig). It was subsequently shown that the progenitor of the plasma cell was a small lymphocyte and that the lymphocyte precursors of plasma cells represented a separate differentiation pathway of cells derived from the avian bursa or mammalian bone marrow (for review see Cooper and Lawton 1974). These B lymphocytes were found to bear membrane-bound Ig as a receptor for antigen (Raff et al. 1970; Pernis et al. 1970). The identification of the precursors of B lymphocytes (see review Kincade 1981; Cooper 1981) proved to be difficult, since it relied on indirect assays, e.g., the ability of fractionated cell populations to differentiate into B lymphocytes after transfer into irradiated hosts, or the in vitro generation of B lymphocytes in organ cultures of fetal liver (e.g. Osmond and Nossal 1974; Owen etal. 1974; Ryser and Vassalli 1974; Melchers etal. 1976). These types of experiments were important in defining the existence and tissue distribution of precursors of B lymphocytes, but were handicapped by the inability to identify the precursor cells directly as well as functionally.