B lymphocytes can be competent antigen-presenting cells for priming CD4+ T cells to protein antigens in vivo.

The potential role of different subsets of APCs to stimulate naive CD4+ T cells to peptide and protein Ags in vivo was examined. Mice lacking B cells (microMT knockout mice) were impaired in their priming to protein but not peptide Ags, suggesting a requirement for B cells in priming to protein Ags in vivo. Experiments designed to determine the ability of splenic dendritic cells (DCs) and B lymphocytes to take up peptide or protein Ags in vivo demonstrated that peptide Ags were taken up preferentially by DCs, whereas proteins were taken up by Ag-specific B cells in vivo. A further examination of the Ag-specific B cells pulsed in vivo with protein Ags revealed a marked up-regulation in surface expression of B7-2 costimulatory molecules, detectable as early as 4 h after Ag administration. Based on their potency in the uptake and processing of protein Ags as well as their ability to up-regulate costimulatory molecules through Ag internalization, we suggest that Ag-specific B cells will be an important APC in priming naive CD4+ T cells to protein Ags in vivo.

Are primed CD4+ T lymphocytes different from unprimed cells?

Primed and unprimed lymphocytes are usually classified as separate subsets of cells, based on phenotypic and functional distinctions. In the case of CD4+ T lymphocytes, primed cells are thought to proliferate more vigorously, quickly and easily, and to release a different profile of cytokines, than their naive equivalent. However, most of these data were obtained from studies in which populations of lymphocytes were compared before and after antigenic stimulation, and therefore did not distinguish between the effects resulting from the clonal expansion of specific precursor cells within such populations and those due to cell differentiation per se. We have investigated the contribution of precursor cell frequency to some of the functional changes observed in populations of CD4+ T cells following antigenic stimulation, using approaches in which antigen-specific precursor frequencies are high in both primary and secondary stimulations: mixed leukocyte reaction responses and cells from alpha beta T cell receptor transgenic mice. Our data suggest that when equivalent numbers of antigen-specific naive and previously primed CD4+ responder T cells are compared, there is no difference in their potency to proliferate but only the previously activated subset can generate cytokines such as interferon-gamma.