A B cell-deficient mouse by targeted disruption of the membrane exon of the immunoglobulin mu chain gene.
Of the various classes of antibodies that B lymphocytes can produce, class M (IgM) is the first to be expressed on the membrane of the developing cells. Pre-B cells, the precursors of B-lymphocytes, produce the heavy chain of IgM (mu chain), but not light chains. Recent data suggest that pre-B cells express mu chains on the membrane together with the 'surrogate' light chains lambda 5 and V pre B (refs 2-7). This complex could control pre-B-cell differentiation, in particular the rearrangement of the light-chain genes. We have now assessed the importance of the membrane form of the mu chain in B-cell development by generating mice lacking this chain. We disrupted one of the membrane exons of the gene encoding the mu-chain constant region by gene targeting in mouse embryonic stem cells. From these cells we derived mice heterozygous or homozygous for the mutation. B-cell development in the heterozygous mice seemed to be normal, but in homozygous animals B cells were absent, their development already being arrested at the stage of pre-B-cell maturation.
Kitamura
D
D
Institute for Genetics, University of Cologne, Germany.
Roes
J
J
Kühn
R
R
Rajewsky
K
K
D000818:Animals; D000944:Antigens, Differentiation, B-Lymphocyte / Q000032:analysis; D001402:B-Lymphocytes / Q000502:physiology*; D015139:Blotting, Southern; D004252:DNA Mutational Analysis; D005434:Flow Cytometry; D005803:Genes, Immunoglobulin; D006410:Hematopoiesis; D007147:Immunoglobulin Light Chains; D054444:Immunoglobulin Light Chains, Surrogate; D007148:Immunoglobulin mu-Chains / Q000235:genetics*; D007153:Immunologic Deficiency Syndromes / Q000235:genetics*; D008562:Membrane Glycoproteins / Q000235:genetics; D051379:Mice; D011947:Receptors, Antigen, B-Cell / Q000235:genetics*
D000944:Antigens, Differentiation, B-Lymphocyte; D007147:Immunoglobulin Light Chains; D054444:Immunoglobulin Light Chains, Surrogate; D007148:Immunoglobulin mu-Chains; D008562:Membrane Glycoproteins; D011947:Receptors, Antigen, B-Cell