Relationships among B Cell Populations Revealed by Global Gene Analysis

Global gene profiling using the data we generated for the ImmGen Consortium allows us to address three issues in B cell function and development: (1) progression through transitional stages in spleen; (2) differences in signaling networks among mature B cell populations; and (3) variation in follicular-type (Fo) B cells with tissue location. For the first issue, we focused on the third transitional stage, T3, asking whether it was a pure population of anergic cells and concluding that only a small fraction of T3 is anergic. For the second, we clustered genes up- and downregulated distinctively in three mature populations, relating these gene sets to differences in B cell receptor signaling that distinguish these subsets. Finally, for the third issue, we identified differences in gene expression in the Fo B cell pool present in spleen, bone marrow, peritoneal cavity, and lymph nodes and found that peritoneal cavity Fo B cells were enriched for apoptosis-related genes compared with spleen, and that lymph node resident cells appeared most functionally mature. These analyses highlight the complexity of gene regulation in different maturation stages and subpopulations of B cells and also the richness of information in the ImmGen data sets.