The tyrosine kinase Lyn is required for B cell development beyond the T1 stage in the spleen: rescue by over-expression of Bcl-2.
We have analyzed the effects of deficiency in the tyrosine kinase Lyn on B cell development using transgenic mice that express a B cell antigen receptor (BCR) of defined specificity (3-83,anti-H-2K(k or b)). In the absence of Lyn, immature B cells are abundant in the bone marrow and spleen up until the T1 stage (IgM(hi) IgD(-) CD21(-)CD23(-)), after which B cell development is severely impaired. The small number of mature B cells that do develop in Lyn-deficient mice express normal levels of the transgenic BCR and lack expression of CD80 and CD86, suggesting they are not activated. In Lyn-deficient animals the presence of a Bcl-2 transgene leads to a dramatic increase in B cell numbers and restores T2 stage (IgM(hi) IgD(hi) CD21(hi) CD23(int)) and mature populations. In 3-83 lyn-/- Bcl-2 Tg mice, a population of lambda-positive cells that also express the 383 idiotype is evident, suggesting that in the absence of lyn isotype exclusion by the transgenic BCR is less efficient. The results indicate that Lyn plays a positive role in the selection and survival of mature B cells in addition to its previously documented negative role in tolerance and B cell activation.
Meade
Josephine
J
The Laboratory of Lymphocyte Signalling and Development, Molecular Immunology Programme, The Babraham Institute, Cambridge, GB.
Fernandez
Claire
C
Turner
Martin
M
D000818:Animals; D016175:B-Lymphocyte Subsets / Q000166:cytology*; D002454:Cell Differentiation; D017637:Clonal Deletion; D019254:Genes, bcl-2; D006183:H-2 Antigens / Q000276:immunology; D007108:Immune Tolerance; D008213:Lymphocyte Activation; D018655:Lymphocyte Count; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000502:physiology*; D011947:Receptors, Antigen, B-Cell / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000502:physiology; D013154:Spleen / Q000166:cytology* / Q000276:immunology; D019061:src-Family Kinases / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
D006183:H-2 Antigens; C024755:H-2K(K) antigen; D019253:Proto-Oncogene Proteins c-bcl-2; D011947:Receptors, Antigen, B-Cell; D011993:Recombinant Fusion Proteins; C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases