Multi-scale analysis of B-cell receptors computing allosteric mechanisms
Antibody-producing B cells can switch the class of immunoglobulin they produce through a process of inducible genomic rearrangement called class-switch recombination (CSR)which changes the constant domain. Ig heavy chain class switching occurs rapidly after activation of mature naïve B cells, resulting in a switch from expressing IgM and IgD to the expression of IgG, IgE, or IgA; this switch improves the ability of antibodies to remove the pathogen that induces the humoral immune response.
The enormous range of possible binding affinities, coupled with the ability to change effector functions for the same variable region sequence, makes them a unique adaptable resource in vivo and in diagnostics and therapeutics. Several studies have reported conformational changes in upon antigen binding, presumably mediated via the hinge region. We suggest that the basic model of Ig structure-function needs to be revisited and conformational long-range effects need to be studied thoroughly.