Distinct subpopulations of IgG memory B cells respond to different molecular forms of the same hapten

Spleen cells from mice primed with the thymus-dependent antigen trinitrophenyl keyhole limpet hemocyanin several months earlier can be cultured in vitro to give vigorous IgG antihapten PFC responses to thymus dependent (TD) and thymus-independent (TI) forms of the same hapten. Here we show that the IgG memory precursors that respond to these two forms of the hapten constitute functionally distinct subpopulations. We have designated these subpopulations as B₁γ and B₂γ to represent secondary precursor cells responding to TI and TD antigens, respectively. Three types of evidence for these subpopulations are presented: 1) In vitro secondary IgG responses to TD and TI forms of the TNP hapten are additive when both forms are added to the same culture. 2) The precursor frequencies for the TD and TI antigens are additive, but addition is not observed between two TD or two TI antigens. 3) Each population can be selectively eliminated by BUdR and light treatment without affecting the other population. The ontogenetic relationships between these subpopulations are discussed in relation to all presently proposed subpopulations B₁μ, B₂μ, B₁γ, and B2γ.