Lyn deficiency affects B‐cell maturation as well as survival

Abstract Lyn, an Src‐family protein tyrosine kinase expressed in B lymphocytes, contributes to initiation of BCR signaling and is also responsible for feedback inhibition of BCR signaling. Lyn‐deficient mice have a decreased number of follicular B cells and also spontaneously develop a lupus‐like autoimmunity. We used flow cytometric analysis, BrdU labeling and our mathematical models of B‐cell population dynamics, to analyze how Lyn deficiency impacts B‐cell maturation and survival. We found that Lyn‐deficient transitional 1 (T1) cells develop normally, but T2 cells develop primarily from the T1 subset in the spleen and fail to also develop directly from BM immature B cells. Lyn‐deficient T2 cells either mature to the follicular B‐cell type at a close to normal rate, or die in this compartment rather than access the T3 anergic subset. The ∼40% of WT follicular cells that were short‐lived exited primarily by joining the T3 anergic subset, whereas the ∼15% Lyn −/− follicular cells that were not long lived had a high death rate and died in this compartment rather than entering the T3 subset. We hypothesize that exaggerated BCR signaling resulting from weak interactions with self‐antigens is largely responsible for these alterations in Lyn‐deficient B cells.