Assembled pre-B cell receptor complexes are retained in the endoplasmic reticulum by a mechanism that is not selective for the pseudo-light chain.
The pre-B cell receptor (BCR) complex, consisting of micro heavy chain, a pseudo-light chain, and the Mb-1/B29 heterodimer, directs the transition to the mature B cell stage. Plasma membrane expression of the pre-BCR is extremely low, despite its presumed signaling function. We have compared assembly and intracellular transport of the pre-BCR complex with that of the BCR complex in mature B cells. Synthesis and assembly rate of pre-BCR and BCR components are comparable. However, the pre-BCR is subject to a highly efficient retention mechanism, which only allows exit of a few percent of the complexes from the endoplasmic reticulum (ER). This small transported pool of pre-BCR complexes is significantly enriched for protein-tyrosine kinase activity, as compared with the ER-localized receptor pool. Accordingly, the Src-related tyrosine kinase Lyn was found in the transported glycoprotein fraction but not in association with ER-localized glycoproteins. Upon introduction of a conventional light chain into pre-B cells, plasma membrane receptor levels increased, but the efficiency of intracellular transport of the receptor complex was not restored to that in mature B cells. This indicates that the ER retention mechanism is not selective for the pseudo-light chain and may be inherent to pre-B cells. We propose that this retention mechanism contributes to the regulation of pre-BCR-mediated signal transduction.
Brouns
G S
GS
Division of Cellular Biochemistry, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.
de Vries
E
E
Neefjes
J J
JJ
Borst
J
J
D001692:Biological Transport; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D006801:Humans; D007147:Immunoglobulin Light Chains / Q000378:metabolism*; D007700:Kinetics; D011498:Protein Precursors / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism*; D015398:Signal Transduction; D014407:Tumor Cells, Cultured
D007147:Immunoglobulin Light Chains; D011498:Protein Precursors; D011947:Receptors, Antigen, B-Cell; D011505:Protein-Tyrosine Kinases