Primary Antibody-Forming Cells and Secondary B Cells Are Generated from Separate Precursor Cell Subpopulations

Abstract Two precursor cell subpopulations have been isolated from the spleen cells of nonimmune mice. The major B cell subpopulation binds high levels of the J11D monoclonal antibody and, upon T cell-dependent antigenic stimulation, gives rise to primary antibody-forming cell clones but not secondary B cells. A minority of the 10%–14% of la + precursors that bind low levels of J11D (J11D lo ) also generate antibody-forming cell clones after primary stimulation. However, over 70% of J11D lo precursors yield no primary antibody-forming cell clones but instead give rise to secondarily responsive B cells. The existence of a distinct precursor cell subpopulation that is responsible for the generation of B cell memory is further evidenced by the distribution of variable region clonotypes among J11D lo primary precursors, which resembles the clonotype patterns of secondary B cells, and by the accumulation of somatic mutations in their clonal progeny.