An idiotypic marker associated with a germ-line encoded κ light chain variable region that predominates the vaccine-induced human antibody response to the Haemophilus influenzae b polysaccharide

Abstract

Human antibodies specific for the Haemophilus influenzae b polysaccharide (Hib PS) frequently express a cross-reactive idiotype (CRI), and commonly utilize a VL region that is the product of the VκII gene A2. To examine further anti-Hib PS V region expression and to determine whether CRI expression is correlated with the VκIIA2 chain, we isolated a monoclonal antibody (MAb) reactive with an idiotypic determinant of anti-Hib PS antibodies. This M Ab inhibited Hib PS binding but did not react with Ig isotypic determinants. The CRI recognized by this MAb, designated HibId-1, was associated with the Hib PS-combining site since the reactivity of the MAb with anti-Hib PS antibodies could be inhibited by Hib PS. HibId-1 was expressed by 17 of 17 clonally purified and sequence-defined anti-Hib PS antibodies having VκIIA2 L chains. In contrast, 0 of 10 anti-Hib PS antibodies having either Vλ, VκI, or V chains expressed HibId-1. Western blot analysis showed that the MAb anti-CRI reacted with isolated anti-Hib PS VκIIA2 L chains but not with H chains or other L chains, indicating that the HibId-l determinant is localized to the VκIIA2 chain, and does not require pairing with H chain for expression. Anti-Hib PS antibodies bearing HibId-l were present in at least 85% of subjects immunized with either free Hib PS or Hib PS coupled to diphtheria toxoid (Hib PS-DT), and comprised on the average 60% of the total vaccine-induced serum anti-Hib PS. HibId-l expression was not related to age at vaccination inasmuch as infants, children, and adults had similar distributions of HibId-1-positive anti-Hib PS after vaccination with Hib PS-DT. HibId-l was expressed at a lower frequency and comprised a smaller fraction of the total anti-Hib PS antibody in adult preimmunization sera as compared to post-Hib PS immunization sera, suggesting that immunization preferentially stimulates HibId-1-positive B cells. These data demonstrate that antibodies bearing HibId-1/VκIIA2 comprise a predominant component of the anti-Hib PS response induced by immunization, and that this pattern of VL expression is established early in ontogeny.