Ontogeny of murine B lymphocytes: sequence of B-cell differentiation from surface-immunoglobulin-negative precursors to plasma cells.

Among bone-marrow-derived (B) lymphocytes exist subpopulations of cells that can be induced to express the markers: surface immunoglobulin (Ig), the antigen associated with the immune response gene (Ia), and the receptor for the third complement component (CR). Inducible cells for the first two markers are found in bone marrow, and inducible cells for all three are in spleen. Experiments were designed to determine whether induction involves a single precursor cell population that on triggering with lipopolysaccharide expresses all three surface markers, or three separate precursor cell populations each of which expresses a single marker. Specific B cell subpopulations were eliminated by treatment with anti-Ig or anti-Ia and complement, or by rosette formation with erythrocytes-antibody-complement followed by differential centrifugation, and surviving cells were subsequently tested for inducibility of the three B cell markers. After anti-Ig cytolysis only Ig, but not Ia and CR, could be induced, implying that the Ia- and the CR-inducible cells are Ig+. Similarly, after anti-Ia cytolysis Ig and Ia but not CR could be induced. Thus, CR-inducible cells must have the Ig+Ia+ phenotype. Elimination of CR+ cells did not affect the induction of Ig, Ia, or CR from their precursors. None of the three elimination experiments affected the conversion of prothymocytes (Thy-1-) to thymocytes (Thy-1+). From these results we propose the hypothesis that the differentiation of B lymphocytes proceeds through at least four distinct stages characterized by the following phenotypes: Ig-Ia-CR- leads to Ig+Ia-CR- leads to Ig+Ia+CR- leads to Ig+Ia+CR+.