Table of Contents Author Guidelines Submit a Manuscript
International Journal of Cell Biology
Volume 2013, Article ID 606703, 9 pages
http://dx.doi.org/10.1155/2013/606703
Review Article

Missing Links in Antibody Assembly Control

Division of Genetics and Cell Biology, San Raffaele Scientific Institute, Via Olgettina 60, 20132 Milan, Italy

Received 3 August 2013; Accepted 7 October 2013

Academic Editor: Christian Appenzeller-Herzog

Copyright © 2013 Tiziana Anelli and Eelco van Anken. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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.