A unique role for the lambda5 nonimmunoglobulin tail in early B lymphocyte development.
Precursor BCR (pre-BCR) signaling governs proliferation and differentiation of pre-B cells during B lymphocyte development. However, it is controversial as to which parts of the pre-BCR, which is composed of Igmu H chain, surrogate L chain (SLC), and Igalpha-Igbeta, are important for signal initiation. Here, we show in transgenic mice that the N-terminal non-Ig-like (unique) tail of the surrogate L chain component lambda5 is critical for enhancing pre-BCR-induced proliferation signals. Pre-BCRs with a mutated lambda5 unique tail are still transported to the cell surface, but they deliver only basal signals that trigger survival and differentiation of pre-B cells. Further, we demonstrate that the positively charged residues of the lambda5 unique tail, which are required for pre-BCR self-oligomerization, can also mediate binding to stroma cell-associated self-Ags, such as heparan sulfate. These findings establish the lambda5 unique tail as a pre-BCR-specific autoreactive signaling motif that could increase the size of the primary Ab repertoire by selectively expanding pre-B cells with functional Igmu H chains.
Vettermann
Christian
C
Division of Molecular Immunology, Department of Internal Medicine III, Nikolaus-Fiebiger-Center for Molecular Medicine, University of Erlangen, Erlangen, Germany.
Herrmann
Kai
K
Albert
Christine
C
Roth
Edith
E
Bösl
Michael R
MR
Jäck
Hans-Martin
HM
D000818:Animals; D001324:Autoantigens / Q000378:metabolism; D001402:B-Lymphocytes / Q000166:cytology*; D007143:Immunoglobulin Heavy Chains; D054444:Immunoglobulin Light Chains, Surrogate / Q000502:physiology*; D007148:Immunoglobulin mu-Chains; D051379:Mice; D008822:Mice, Transgenic; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism; D015398:Signal Transduction
D001324:Autoantigens; D007143:Immunoglobulin Heavy Chains; D054444:Immunoglobulin Light Chains, Surrogate; D007148:Immunoglobulin mu-Chains; D011947:Receptors, Antigen, B-Cell