A Microfluidic Strategy to Capture Antigen‐Specific High‐Affinity B Cells

Abstract

Assessing B cell affinity to pathogen‐specific antigens prior to or following exposure could facilitate the assessment of immune status. Current standard tools to assess antigen‐specific B cell responses focus on equilibrium binding of the secreted antibody in serum. These methods are costly, time‐consuming, and assess antibody affinity under zero force. Recent findings indicate that force may influence BCR‐antigen binding interactions and thus immune status. Herein, a simple laminar flow microfluidic chamber in which the antigen (hemagglutinin of influenza A) is bound to the chamber surface to assess antigen‐specific BCR binding affinity of five hemagglutinin‐specific hybridomas from 65 to 650 pN force range is designed. The results demonstrate that both increasing shear force and bound lifetime can be used to enrich antigen‐specific high‐affinity B cells. The affinity of the membrane‐bound BCR in the flow chamber correlates well with the affinity of the matched antibodies measured in solution. These findings demonstrate that a microfluidic strategy can rapidly assess BCR‐antigen‐binding properties and identify antigen‐specific high‐affinity B cells. This strategy has the potential to both assess functional immune status from peripheral B cells and be a cost‐effective way of identifying individual B cells as antibody sources for a range of clinical applications.