Germinal center selection and the antibody response to influenza

Abstract

In this Minireview, we discuss basic aspects of germinal center biology in the context of immunity to influenza infection and speculate on how the simultaneous evolutionary races of virus and antibody may impact our efforts to design a universal influenza vaccine.

Figure 1

(A) Residue conservation among seasonal H1 HA isolates (1975–2005). Conservation is shown for one monomer, on a scale from blue (most conserved) to white (most variable). Red residues indicate common glycosylation sites. The RBS is marked with a star. Image courtesy of Stephen C. Harrison. (B) Overview of affinity maturation in the GC. Cyclic migration of B cells between light and dark zones drives affinity maturation. Prior to GC entry and upon positive selection, B cells can differentiate into the PC or memory fates. (C) Proposed model for reestablishment of immunodominance to strain-specific epitopes. Top, exposure to Strain 1 of influenza generates a response mostly focused on immunodominant, Strain 1-specific epitopes (red), but also induces a subdominant crossreactive response (green). Middle, exposure to a divergent Strain 2 will initially reactivate cross-reactive memory cells (green) from the response to Strain 1, generating a “broad” response, but will also prime Strain 2-specific clones de novo, which will eventually outcompete the crossreactive clones. Bottom, re-exposure to Strain 2 will preferentially recall Strain 2-specific clones, reinstating immunodominance.