I understand that the cell class switches to change the type of immunoglobulin it is producing. The B-cell produces the membrane bound B-cell receptor (BCR) while the plasma cell produces the the secreted form of Ig, the antibody. Now, the isotypes are different in their constant regions and I'm assuming switching only matters if it is an antibody. (differences in avidity, permeability, antibody receptors, etc.)
How would a B-cell receptor (membrane bound Ig) even benefit from class switching? Does class switching even happen in activated B-cells? Or is it a process limited to plasma cells? I read up that BCR also has the 5 isotypes.
What are the specific chronological milestones at which class switching happens in plasma cells and B-cells (if it does)?
Class switching occurs in B cells that are participating in a germinal center reaction, after being activated by antigen and a cognate T cell. (Note that this is the classical paradigm for responses to T-dependent antigens, and that there are exceptions and examples of germinal center-independent class switching). After a B cell has undergone somatic hypermutation and class switching of its immunoglobulin gene, it may or may not be positively selected to differentiate into a plasmablast. Plasmablasts proliferate rapidly before terminal differentiation to plasma cells, which secrete affinity matured, class-switched antibody. So in other words, class switch recombination is largely restricted to activated, germinal center B cells, and as far as I know, does not occur extensively in differentiated plasma cells. Here's a review on germinal centers that describes the progression of B cells within them:
http://www.nature.com/nri/journal/v8/n1/full/nri2217.html
As for surface expression of isotypes other than IgM, let me point out two things: One, remember that when CSR occurs, it involves excision of the intervening DNA between the rearranged VDJ exon and the constant exons being switched to, meaning that they are deleted from the allele. Thus, a B cell that has class switched from IgM to, say, IgG would delete the IgM and IgD heavy chain exons on that allele, and would be restricted to IgG (or IgE and IgA, which lie downstream). So it isn't necessarily a question of whether there is a benefit to expression of IgM versus IgG on the surface for the cell, but rather that there is an immense benefit immunologically in diversifying antibody function through switching to different isotypes.
Second, at least for comparison of IgM and IgD, they seem to possess different signaling properties that may alter the outcome of antigen engagement for the cell. For details, see this review:
http://www.ncbi.nlm.nih.gov/pubmed/?term=control+of+B+cell+responsiveness+by+isotype+and+structural
I hope this helps!
-Max
Thanks! But I've something that's still not clarified. According to this image, http://www.nature.com/nri/journal/v8/n1/fig_tab/nri2217_F1.html
the initial B-cell which entered the germinal centre already had a BCR on it which I'm assuming is an IgM. So when the B-cell is selected to become a plasma cell in the light zone, it says, a CSR has to occur. So if the BCRs were IgM/D and the cell had to class switch, it would have to choose to produce one of the downstream IgG/A/E antibodies only. Yet the primary response is IgM antibody mediated.
If the B cells bearing IgM had already class switched (to their possible downstream counterparts), how can the primary response be IgM dominant? How could IgM antibodies come from class switched plasma cells?
This is because the germinal center response does not occur immediately. Generally speaking, if there is no pre-existing immunity to an antigen, then it follows that the initial humoral response to that antigen is mediated by naive, non class-switched follicular B cells, that give rise to short-lived plasmablasts which secrete IgM independently of germinal center formation (Marginal zone and B-1 B cells can also contribute to these responses). This occurs within the first few days of exposure to a novel antigen. Then, once a week or more has gone by, germinal centers form in secondary lymphoid organs, resulting in the production of class-switched, affinity-matured memory cells and plasma cells. At this point, the humoral responses ceases to be dominated by IgM, and serum levels of class-switched antibodies rise.
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