Thursday, October 1, 2015

B cell activation by antigen promotes desegregation of IgM and IgD islands

There are two models of B cell activation. In one model, B cell activation is promoted by clustering of individual IgM molecules. Second model, however, argues that B cell activation is promoted by de-clustering of IgM "islands". This second model is mainly based on research by Micheal Reth's lab.

To study B cell receptor architecture on resting or activated B cells, the authors have used 3 different but complementary approaches: (1) two-color direct stochastic optical reconstruction microscopy (dSTORM), (2) two marker transmission electron microscopy (TEM) and (2) proximity ligation assay (PLA). 

First, the authors showed that on resting B cells, both IgM and IgD are segregated into islands containing on average 30 IgM and 48 IgD molecules, respectively.

Next, the authors showed that upon activation, both IgM and IgD islands show reduction of number of receptors per islands, implying that individual IgM or IgD receptors are leaving the islands.  

Interestingly, the authors showed that both IgM and IgD islands could independently respond to the antigen.  

In addition, detection of IgM and IgD (co)-localisation by TEM after antigen exposure confirmed receptors meetup (receptors were detected by secondary antibodies conjugated to two different size gold particles).  

In summary, this study supports the hypothesis that upon B cell activation IgM and IgD receptors leave "home islands" and move close to each other, thus facilitating sharing of downstream signaling molecules. This study is a "biochemical" study that does not incorporate "biological" significance of BCR dissociation, however.   

David Usharauli

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