Immunoglobulin gene rearrangement in B cell deficient mice generated by targeted deletion of the JH locus.
B lymphocyte differentiation is characterized by an ordered series of Ig gene assembly and expression events. In the majority of normal B cells, assembly and expression of Ig heavy (H) chain genes precedes that of light (L) chain genes. To determine the role of the Ig heavy chain protein in B cell development and L chain gene rearrangement, we have generated mice that cannot assemble Ig H chain genes as a result of targeted deletion of the JH gene segments in embryonic stem cells. Mice homozygous for this deletion are devoid of slg+ B cells in the bone marrow and periphery. B cell differentiation in these mice is blocked at the large, CD43+ precursor stage. However, these precursor B cells do assemble kappa L chain genes at a low level in the absence of mu H chain proteins. These data demonstrate that rearrangement and expression of the mu H chain gene is not absolutely required for kappa L chain gene rearrangement in vivo. Expression of mu chains may facilitate either efficient L chain gene rearrangement or the survival of cells that have rearranged light chain genes by promoting the differentiation of large, CD43+ to small, CD43- pre-B cells.
Chen
J
J
Howard Hughes Medical Institute, Children's Hospital, Boston, MA.
Trounstine
M
M
Alt
F W
FW
Young
F
F
Kurahara
C
C
Loring
J F
JF
Huszar
D
D
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology; D001483:Base Sequence; D004247:DNA / Q000235:genetics; D015322:Gene Rearrangement, B-Lymphocyte; D015328:Gene Rearrangement, B-Lymphocyte, Light Chain; D006412:Hematopoietic Stem Cells / Q000276:immunology; D006720:Homozygote; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007133:Immunoglobulin Joining Region / Q000235:genetics; D051379:Mice; D008969:Molecular Sequence Data; D011995:Recombination, Genetic; D017384:Sequence Deletion
D007143:Immunoglobulin Heavy Chains; D007133:Immunoglobulin Joining Region; D004247:DNA