Single-cell transcriptomic and immunoglobulin profiling in WT and IkB-deficient mouse early B cell progenitor and precursor populations

Further analysis revealed that the differentiation hypermorph leads to diminished mature cell populations given that differentiation pauses are essential for population expansion. Transcriptomic profiling at single-cell resolution revealed that RelA dynamic dysregulation resulted in an accelerated progression of transcriptomic cell states that are not in synch with the classically defined progenitors and – importantly – override the preBCR checkpoint.

As this is a major quality control step to ensure proper immunoglobulin heavy chain recombination, the mutant triggers premature κ-light chain recombination, resulting in B-cells with nonfunctional immunoglobulin. Our findings establish a new paradigm for how aging and inflammation impact humoral immunity via dysregulation of RelA dynamics: accelerated differentiation diminishes the size and the quality of the B-cell pool available for adaptive immune responses.