Developmental control of IgM secretion

In the case of IgM and IgA, the basic H2L2 structure is further assembled into polymers which contain J chain, a small cysteine-rich glycoprotein synthesized by plasma cells, but not by resting B lymphocytes. Only polymeric IgM is secreted, despite the fact that the major intracellular form is |x2L2. Thus, IgM (and IgA) undergo a further level of control, which blocks secretion of nonpolymeric molecules. This editing step depends on disulfide interchange reactions, which involve the cysteine residue found at the penultimate position of both n_s and as chains. This residue is responsible for the intersubunit disulfide bonds which stabilize the polymeric structure. In assembly intermediates the unbound SH group may interact with ER resident proteins, thereby blocking then-transport to the Golgi. Thus, IgM is subject to a dual editing process which allows plasma cells to secrete only polymers. First, jjl-L association is controlled by-interactions between BiP and sequences in the CjjlI; then, disulfide interchange reactions control polymerization.

In B lymphocytes, polymerization is very inefficient, a finding that explains why IgM is not secreted. The requirement for polymerization might also explain why, also in myelomas, secretion of IgM is rather slow and inefficient compared with IgG. If the C-terminal cysteine of the m chain is replaced by serine, the rate and efficiency of IgM secretion is increased, and intracellular degradation reduced. Furthermore, these mutant monomeric IgMs are secreted also by B cells, indicating that the presence of a developed ER is not per se necessary for secretion of immunoglobulin molecules.

As polymeric IgM contains J chains, it has been proposed that the failure of B cells to secrete IgM correlates with the absence of J chain synthesis. However, since B cell lines have been isolated which synthesize J chain and yet do not secrete IgM, and nonlymphoid transfectants secrete polymeric IgM lacking J chains, the latter appear to be neither essential nor sufficient for IgM secretion. Knock-out mice that lack J chains have high levels of IgA (mainly monomeric) and of hexameric IgM in the serum. Hence, J chain seems to play a key role in 1) determining the size of polymeric IgM (pentamers predominate in the presence of J chain), and 2) facilitating the transcytosis of polymeric Igs across epi-thelia. The problem of why B cells do not secrete IgM may thus be reduced to the single question as to why in B cells polymerization is so inefficient. Differentiation into IgM secreting plasma cells is accompanied by major changes in the ER and by a much higher rate of synthesis of ¡a, and L chains. These events might include modification(s) of the redox potential along the secretory pathway which would favor polymerization.

How To Bolster Your Immune System

How To Bolster Your Immune System

All Natural Immune Boosters Proven To Fight Infection, Disease And More. Discover A Natural, Safe Effective Way To Boost Your Immune System Using Ingredients From Your Kitchen Cupboard. The only common sense, no holds barred guide to hit the market today no gimmicks, no pills, just old fashioned common sense remedies to cure colds, influenza, viral infections and more.

Get My Free Audio Book


Post a comment