Missing links in antibody assembly control

Tiziana Anelli, Eelco Van Anken

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Fidelity of the humoral immune response requires that quiescent B lymphocytes display membrane bound immunoglobulin M (IgM) on B lymphocytes surface as part of the B cell receptor, whose function is to recognize an antigen. At the same time B lymphocytes should not secrete IgM until recognition of the antigen has occurred. The heavy chains of the secretory IgM have a C-terminal tail with a cysteine instead of a membrane anchor, which serves to covalently link the IgM subunits by disulfide bonds to form " pentamers" or "hexamers." By virtue of the same cysteine, unassembled secretory IgM subunits are recognized and retained (via mixed disulfide bonds) by members of the protein disulfide isomerase family, in particular ERp44. This so-called "thiol-mediated retention" bars assembly intermediates from prematurely leaving the cell and thereby exerts quality control on the humoral immune response. In this essay we discuss recent findings on how ERp44 governs such assembly control in a pH-dependent manner, shuttling between the cisGolgi and endoplasmic reticulum, and finally on how pERp1/MZB1, possibly as a co-chaperone of GRP94, may help to overrule the thiol-mediated retention in the activated B cell to give way to antibody secretion.

Original languageEnglish
Article number606703
JournalInternational Journal of Cell Biology
DOIs
Publication statusPublished - 2013

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Immunoglobulin M
B-Lymphocytes
Immunoglobulin Subunits
Antibodies
Humoral Immunity
Sulfhydryl Compounds
Disulfides
Cysteine
Protein Disulfide-Isomerases
Antigens
Immunoglobulin Heavy Chains
B-Cell Antigen Receptors
Endoplasmic Reticulum
Quality Control
Membranes

ASJC Scopus subject areas

  • Cell Biology

Cite this

Missing links in antibody assembly control. / Anelli, Tiziana; Van Anken, Eelco.

In: International Journal of Cell Biology, 2013.

Research output: Contribution to journalArticle

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