Abstract
As the primary antibody and with increasing interest as a therapeutic antibody, IgM is also the largest antibody structure among the five major human isotypes. Spontaneously forming oli-gomers as pentamer and hexamers, IgM has avidity effects that could compensate for lower interactions as monomers. With recent findings of effects of the heavy chain constant region affecting antigen binding and the VH families of the V-regions affecting FcR engagement, we CDR grafted Trastuzumab and Pertuzumab CDRs to VH1-7 IgMs for biolayer interferometry investigations. From our panel of the 14 IgM variants, we found evidence of the V-regions holistically affecting FcμR binding and for the IgM C-region affecting Her2 engagements, mediated by the V-regions holistically and also by protein L binding at the light chain V-region. These findings suggest the oligomerization effect of IgMs that may affect both FcμR and antigen binding that are different from the other monomeric isotypes with relevance to guiding the development and protein engineering of IgM therapeutics.
Competing Interest Statement
The authors have declared no competing interest.