Tracking and Characterizing Human B-Cell Responses in Rhinovirus Infection

Rationale: Human rhinoviruses (RV) account for 31 million estimated cases of the common cold per year within the US, and trigger disease exacerbations in allergic asthmatics.  Adaptive immunity to RV does not provide durable protection owing partly to considerable diversity of RV strains.  Here we describe circulating lymphocytes in the context of RV infection, exploring factors that determine the quality of the humoral response.

Methods: Mass cytometry was used to capture fluctuations in discrete B-cell populations during an experimental RV-16 infection in allergic asthmatics.  The findings were used to inform the design of an antigen-specific fluorescence-based flow cytometry panel in order to further interrogate the B-cell compartment in relation to RV infection.

Results: B-cell antigen-specificity was validated in blood from control subjects and atopics using fluorescent tetramers of tetanus toxoid and Der p 1, respectively. We readily identified naïve B-cells (IgD+), plasmablasts (CD20-, CD38+), and 2 discrete memory populations that differentially expressed the follicular-homing marker, CXCR5.  Whereas CXCR5+ memory cells expressed CD27 and diverse isotypes, their CXCR5- counterparts were CD27lo, expressed the transcription factor T-bet, and lacked IgM.  This latter phenotype disappeared from the blood in conjunction with memory T-cells during the acute phase of RV infection, while plasmablasts that primarily expressed IgA were expanded.

Conclusions: Our findings are consistent with the presence of pre-existing memory B-cells that are poised for reactivation by cognate antigen stimulation, potentially with or without T-cell help.  Further work is necessary to determine the B-cell mechanisms that promote virus-neutralizing activity, including how T-cells might instruct the protectiveness of antibodies produced.