Removal of the BiP-retention domain in Cmicro permits surface deposition and developmental progression without L-chain.
Nascent, full length, immunoglobulin (Ig) heavy (H)-chains are post-translationally associated with H-chain-binding protein (BiP or GRP78) in the endoplasmic reticulum (ER). The first constant (C) domain, CH1 of a C gene (Cmu, Cgamma, Calpha), is important for this interaction. The contact is released upon BiP replacement by conventional Ig light (L)-chain (kappa or lambda). Incomplete or mutated H-chains with removed variable (VH) and/or C(H)1 domain, as found in H-chain disease (HCD), can preclude stable BiP interaction. Progression in development after the preB cell stage is dependent on surface expression of IgM when association of a micro H-chain with a L-chain overcomes the retention by BiP. We show that IgM lacking the BiP-binding domain is displayed on the cell surface and elicits a signal that allows developmental progression even without the presence of L-chain. The results are reminiscent of single chain Ig secretion in camelids where developmental processes leading to the generation of fully functional H-chain-only antibodies are not understood. Furthermore, in the mouse the largest secondary lymphoid organ, the spleen, is not required for H-chain-only Ig expression and the CD5 survival signal may be obsolete for cells expressing truncated IgM.
Zou
Xiangang
X
The Babraham Institute, Babraham, Cambridge CB22 3AT, United Kingdom.
Smith
Jennifer A
JA
Corcos
Daniel
D
Matheson
Louise S
LS
Osborn
Michael J
MJ
Brüggemann
Marianne
M
D000818:Animals; D000954:Antigens, Surface / Q000378:metabolism*; D001402:B-Lymphocytes / Q000276:immunology / Q000502:physiology; D002454:Cell Differentiation / Q000235:genetics; D000091342:Endoplasmic Reticulum Chaperone BiP; D017353:Gene Deletion; D015322:Gene Rearrangement, B-Lymphocyte / Q000235:genetics*; D006360:Heat-Shock Proteins / Q000276:immunology / Q000378:metabolism* / Q000502:physiology; D007127:Immunoglobulin Constant Regions; D007147:Immunoglobulin Light Chains / Q000235:genetics / Q000502:physiology*; D007075:Immunoglobulin M / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D007148:Immunoglobulin mu-Chains / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D018832:Molecular Chaperones / Q000276:immunology / Q000378:metabolism* / Q000502:physiology; D017434:Protein Structure, Tertiary / Q000235:genetics / Q000502:physiology
D000954:Antigens, Surface; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins; C000717248:Hspa5 protein, mouse; D007127:Immunoglobulin Constant Regions; D007147:Immunoglobulin Light Chains; D007075:Immunoglobulin M; D007148:Immunoglobulin mu-Chains; D018832:Molecular Chaperones