B cell development in mice with a defective lambda 5 gene.
The surrogate light chain encoded by the two pre-B cell-specific genes VpreB and lambda 5 plays a critical role in B cell development of the mouse. It has been shown that targeted disruption of the lambda 5 gene results in a depletion of B220+ CD43- IgM-pre-B cells in bone marrow, and in a delayed appearance both of CD5+ as well as CD5- surface immunoglobulin (sIg)+ B cells in the periphery. In this report we show that DHJH-rearranged B220- and B220+, CD43+, c-kit+, sIgM- pro- and pre-B-I cells with long-term capacity to proliferate in vitro on stromal cells in the presence of interleukin-7 are present in normal numbers in the bone marrow of lambda 5 T/lambda 5 T mice at various ages. They express normal levels of VpreB mRNA but, in contrast to normal pre-B-I cells, do not express surrogate light chain on their surface. Pre-B-I cells from fetal liver and bone marrow of lambda 5 T/lambda 5 T mice differentiate with normal kinetics and in normal numbers to sIg+, mitogen-reactive B cells. These results suggest that the delayed generation of sIg+ B cells in the peripheral, mature compartments of CD5+ and CD5- cells could be accounted for by the daily production of approximately 5 x 10(5) sIg+ B cells from the pre-B-I cell pool in the absence of a normal pool of pre-B-II cells.
Rolink
A
A
Basel Institute for Immunology, Switzerland.
Karasuyama
H
H
Grawunder
U
U
Haasner
D
D
Kudo
A
A
Melchers
F
F
D000818:Animals; D000944:Antigens, Differentiation, B-Lymphocyte / Q000032:analysis; D000954:Antigens, Surface / Q000032:analysis; D016175:B-Lymphocyte Subsets / Q000166:cytology*; D005803:Genes, Immunoglobulin; D006412:Hematopoietic Stem Cells / Q000166:cytology; D007147:Immunoglobulin Light Chains; D054444:Immunoglobulin Light Chains, Surrogate; D007146:Immunoglobulin lambda-Chains / Q000235:genetics / Q000378:metabolism*; D007148:Immunoglobulin mu-Chains / Q000235:genetics / Q000378:metabolism; D016130:Immunophenotyping; D015851:Interleukin-7 / Q000494:pharmacology; D017493:Leukocyte Common Antigens; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D016254:Mutagenesis, Insertional; D011518:Proto-Oncogene Proteins / Q000032:analysis; D019009:Proto-Oncogene Proteins c-kit; D011947:Receptors, Antigen, B-Cell / Q000502:physiology
D000944:Antigens, Differentiation, B-Lymphocyte; D000954:Antigens, Surface; D007147:Immunoglobulin Light Chains; D054444:Immunoglobulin Light Chains, Surrogate; D007146:Immunoglobulin lambda-Chains; D007148:Immunoglobulin mu-Chains; D015851:Interleukin-7; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D011518:Proto-Oncogene Proteins; D011947:Receptors, Antigen, B-Cell; D019009:Proto-Oncogene Proteins c-kit; D017493:Leukocyte Common Antigens