B-cell restriction – an alternative piece to the puzzle

Gershoni, Jonathan M.

Somatic hyper-mutation accompanied with multiple rounds of immunogen/B-cell encounters are the steps that lead to affinity maturation. 14 An initial binding event of a pathogen by a B-cell launches clonal expansion and the production of lead IgM antibodies. Initially, the efficacy of these relatively broad-spectrum weak binders to counteract invading pathogens lies in the avidity gained by the deca-valency of IgM. 15 However, as AID-mediated mutagenesis of the variable domains kicks in, the fit of the CDR loops to the idiosyncrasies of the epitope being bound gradually improves. Mutation, followed by the selection of those B-cell clones that gain ever-increasing affinity, drive the antibody to perfection and the ability to continually clear the pathogen as its concentration ever decreases. Ultimately, an optimized CONTACT Jonathan M. Gershoni, antibody is produced whose paratope neatly complements the nooks and crannies of the epitope with precision, exhibiting binding affinities of KD < 10 −9 -10 −10 M. 14,16-18 • The deposit and recall of mature memory cells. This process of developing perfected B-cell responses takes time. However, when naturally encountering a virulent pathogen, this time can be critical, giving the pathogen an opportunity to replicate and establish a lifethreatening infection. Vaccination, on the other hand, affords our immune system the chance to study harmless versions of the pathogen, elicit clonal expansion of select B-cells and the ability to go through repeated rounds of somatic hypermutation to perfect affinity matured antibodies. 1 The success of vaccination lies in the option to train effective B-cells and store mature memory cells in the absence of disease and to recall them upon demand. The archive of perfected memory B-cell clones ensures that future encounters with virulent field isolates of the pathogen are met with an immediate B-cell frenzy secreting perfectly matched antibodies that intercept the pathogens and knock them out before infection sets in and disease ensues.