Eileen Goodwin (Mentors: Scott Hensley, PhD & Laurence Eisenlohr, VMD, PhD)

"Effects of serum antibody on de novo B cell responses to influenza”

Eileen Goodwin, Scott Hensley, Laurence Eisenlohr

In adults, the immune response to influenza is dominated by antibodies generated to prior exposures with a notable scarcity of new strain-specific antibodies, a long-studied phenomenon termed “original antigenic sin”. Most explanations focus on the relative fitness of memory versus naïve B cells, but the role of serum antibody in this phenomenon has been less thoroughly examined. In a mouse model, we interrogated the effects of circulating anti-hemagglutinin (HA) antibody on B cell responses to influenza vaccination in the absence of memory B cells. We found that circulating HA-specific antibody inhibits production of HA-specific IgM and HA-specific plasmablasts. Circulating HA-specific antibody also reduces participation of HA-specific B cells in germinal centers but does not alter overall germinal center B cell frequency, suggesting an antigen-specific effect. Mice still produce HA-specific IgG in the presence of HA antibody, but the subclass composition is altered to favor IgG1 production. Preliminary data suggests that antibody responses to other influenza proteins (exemplified by nucleoprotein, NP) are not inhibited by HA-specific antibody; however, these responses also show augmented class switching to IgG1. This work points to both antigen-specific and nonspecific mechanisms whereby circulating antibody modulates de novo immune responses.