title: 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.
authors: The Mina and Everard Goodman Faculty of Life Sciences, Bar Ilan University, Ramat-Gan, Israel.
authors: Gitit
authors: G
authors: Shahaf
authors: Andrew J
authors: AJ
authors: Gross
authors: Michal
authors: M
authors: Sternberg-Simon
authors: Deborah
authors: D
authors: Kaplan
authors: Anthony L
authors: AL
authors: DeFranco
authors: Ramit
authors: R
authors: Mehr
mesh_terms: D000818:Animals; D016175:B-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002469:Cell Separation; D002470:Cell Survival / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D005434:Flow Cytometry; D007075:Immunoglobulin M / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008962:Models, Theoretical; D054448:Precursor Cells, B-Lymphoid / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D011947:Receptors, Antigen, B-Cell / Q000276:immunology; D017455:Receptors, IgE / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology; D013154:Spleen / Q000473:pathology; D019061:src-Family Kinases / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
chemical_list: D007075:Immunoglobulin M; D011947:Receptors, Antigen, B-Cell; D017455:Receptors, IgE; C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases