The B cell repertoire revealed by major histocompatibility complex-specific helper T cells. I. Frequencies of a genetically defined V region marker among mitogen- and T helper cell-reactive B lymphocytes in normal and immunized mice.

Abstract

The quantitative description of the V gene repertoire in various steady states is of paramount importance not only for our understanding of the laws that govern the selection of the available repertoire from the pool of germ line encoded V genes, but also for predicting the consequences of specific and nonspecific immunological manipulations.The numbers of cell precursors of clones secreting Ig with a given specificity cannot be directly evaluated in mass cultures or in adoptive transfer experiments, as the number of antibody-producing plaque-forming cells (PFC) i or antibody titer depends on both the number of reacting B cells and on clone sizes. Antibody repertoires can therefore only be estimated under limiting dilution conditions in which lymphocytes are either specifically or polyclonally activated. As it has been generally assumed that B cells sensitive to lipopolysaccharide (LPS) express the total repertoire of V region sets on Ig molecules, this ligand has been considered the mitogen of choice for frequency determinations (1).Recently, however, it has become evident that the repertoire of LPS-sensitive B cells is not completely representative of the total set of Ig specificities in one animal's B cell population and, in addition, it has also been proved that V genes are not, as previously thought, randomly distributed among functional B cell subsets (2, 3). The most important limitation placed on the analysis of the repertoire of LPS-reactive precursor cells, however, is that these lymphocytes may mainly represent newly born short-lived B cells not yet selected into the functional immune system (4-7). This selection may in fact require further differentiation, which enables the cells to become longer living and capable of collaborating with T cells.In order to obtain accurate information on the set of V genes of cells selected

Induction of a cationic shift in IgG anti-DNA autoantibodies. Role of T helper cells with classical and novel phenotypes in three murine models of lupus nephritis.

“…In other cases, polyclonal mitogens, such as LPS, were used to induce anti-DNA antibody production (41) . However, LPS stimulates only an immature subset of B cells that are different from those induced by activated Th cells (43), and indeed, cationic anti-DNA antibodies could not be induced by LPS stimulation (Fig . 4B).…”