A truncated heavy chain protein relieves the requirement for surrogate light chains in early B cell development.
Early B cell development depends upon the surface expression of Ig heavy chain protein (mu) in a signaling complex known as the pre-B cell receptor (pre-BCR). In addition to mu, the pre-BCR consists of the surrogate light chains VpreB and lambda5 and the transmembrane signal transduction proteins Ig-alpha and Ig-beta. Expression of this complex is associated with changes in surface marker expression, gene transcription, and Ig gene rearrangement. Mutations preventing the expression of either mu or lambda5 result in developmental arrest, but the precise roles of the various components of the pre-BCR remain unclear. Using mice transgenic for a surface-expressed, but truncated, form of mu that cannot associate with surrogate light chains, we have studied the role of surrogate light chains in B cell development. We found that expression of the truncated mu transgene resulted in changes in surface marker expression, germline kappa locus transcription, and V(D)J recombinase targeting indistinguishable from those induced by intact mu protein. These experiments lead us to conclude that surrogate light chains, while necessary for the assembly of the wild-type pre-BCR, are not directly involved in pre-BCR signaling or otherwise required for early B cell development.
Shaffer
A L
AL
Department of Molecular Biology and Genetics, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Schlissel
M S
MS
D000818:Animals; D000954:Antigens, Surface / Q000378:metabolism; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology; D015322:Gene Rearrangement, B-Lymphocyte; D006412:Hematopoietic Stem Cells / Q000276:immunology / Q000378:metabolism; D007143:Immunoglobulin Heavy Chains / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D007147:Immunoglobulin Light Chains / Q000235:genetics* / Q000378:metabolism; D054444:Immunoglobulin Light Chains, Surrogate; D007146:Immunoglobulin lambda-Chains / Q000378:metabolism; D007148:Immunoglobulin mu-Chains / Q000235:genetics / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008822:Mice, Transgenic; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism; D014158:Transcription, Genetic / Q000276:immunology
D000954:Antigens, Surface; D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains; D054444:Immunoglobulin Light Chains, Surrogate; D007146:Immunoglobulin lambda-Chains; D007148:Immunoglobulin mu-Chains; D008562:Membrane Glycoproteins; D011947:Receptors, Antigen, B-Cell