Truncated immunoglobulin Dmu causes incomplete developmental progression of RAG-deficient pro-B cells.
Early stages of B cell development are dependent on the expression of a pre-B cell receptor (BCR), composed of a mu heavy chain (HC) in association with surrogate light chain (SLC) proteins and the signaling molecules, Igalpha and Igbeta. During the formation of the variable region of the mu chain by somatic gene rearrangement, a truncated form of the mu protein (called Dmu) is sometimes produced by the rearrangement of a D(H) segment to a J(H) segment using one of three reading frames (designated rf2). When a Dmu protein is formed, subsequent B cell development is blocked by down-regulation of further HC rearrangements, so that a full-length muHC cannot be formed. In this study, we demonstrate that in recombinase activating gene (RAG)-2-deficient B220(+) CD43(+) pro-B cells in which B lymphopoiesis has been arrested at fraction C, transgenic expression of Dmu promoted partial developmental progression to fraction C', but was unable to mediate the pro-B to pre-B cell transition to fraction D effected by full-length muHC protein. These data suggest that the intracellular signaling pathways engaged by the Dmu pre-BCR are insufficient to facilitate the expansion and/or survival of pre-B cells, and are distinct from those engaged by the pre-BCR-containing full-length muHC.
Malynn
Barbara A
BA
The Center for Blood Research, Harvard Medical School, Boston, MA 02115, USA.
Shaw
Albert C
AC
Young
Faith
F
Stewart
Valerie
V
Alt
Frederick W
FW
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000276:immunology*; D007147:Immunoglobulin Light Chains / Q000235:genetics / Q000276:immunology; D007148:Immunoglobulin mu-Chains / Q000235:genetics / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D054420:Pre-B Cell Receptors; D011947:Receptors, Antigen, B-Cell; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology
D004268:DNA-Binding Proteins; D007147:Immunoglobulin Light Chains; D007148:Immunoglobulin mu-Chains; D008562:Membrane Glycoproteins; D054420:Pre-B Cell Receptors; C499308:Rag2 protein, mouse; D011947:Receptors, Antigen, B-Cell; C064655:V(D)J recombination activating protein 2