Block in development at the pre-B-II to immature B cell stage in mice without Ig kappa and Ig lambda light chain.
Silencing individual C (constant region) lambda genes in a kappa(-/-) background reduces mature B cell levels, and L chain-deficient (lambda(-/-)kappa(-/-)) mice attain a complete block in B cell development at the stage when L chain rearrangement, resulting in surface IgM expression, should be completed. L chain deficiency prevents B cell receptor association, and L chain function cannot be substituted (e.g., by surrogate L chain). Nevertheless, precursor cell levels, controlled by developmental progression and checkpoint apoptosis, are maintained, and B cell development in the bone marrow is fully retained up to the immature stage. L chain deficiency allows H chain retention in the cytoplasm, but prevents H chain release from the cell, and as a result secondary lymphoid organs are B cell depleted while T cell levels remain normal.
Zou
Xiangang
X
Laboratory of Developmental Immunology, The Babraham Institute, Babraham, Cambridge, United Kingdom.
Piper
Tony A
TA
Smith
Jennifer A
JA
Allen
Nicholas D
ND
Xian
Jian
J
Brüggemann
Marianne
M
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology* / Q000473:pathology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D003593:Cytoplasm / Q000235:genetics / Q000276:immunology; D017353:Gene Deletion; D020868:Gene Silencing / Q000276:immunology; D005819:Genetic Markers / Q000276:immunology; D007127:Immunoglobulin Constant Regions / Q000235:genetics; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007145:Immunoglobulin kappa-Chains / Q000235:genetics*; D007146:Immunoglobulin lambda-Chains / Q000235:genetics*; D007148:Immunoglobulin mu-Chains / Q000235:genetics; D008231:Lymphopenia / Q000235:genetics / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D010446:Peptide Fragments / Q000235:genetics; D013234:Stem Cells / Q000166:cytology* / Q000276:immunology* / Q000473:pathology
D005819:Genetic Markers; D007127:Immunoglobulin Constant Regions; D007143:Immunoglobulin Heavy Chains; D007145:Immunoglobulin kappa-Chains; D007146:Immunoglobulin lambda-Chains; D007148:Immunoglobulin mu-Chains; D010446:Peptide Fragments