VH3-family genes are predominately used in gene transcripts of allergic donors
The variable region of the heavy chain gene transcript consists of recombined V, D and J genes. The V gene accounts for most nucleotides of the variable region and contributes, besides D and J genes, to the CDR3 region. Hence, heavy chain V gene lineage can greatly affect B-cell receptor specificity and affinity. In line with B-cell repertoires described in literature26, VH3-family genes were observed to dominate across all groups, with a shift to higher proportions (89%, mainly IGHV3-30, VH3-23 and VH3-72) in allergic donors (X2 (2, n =183)=23.67, p< .0001). This significant difference was still present upon neglecting redundant sequences from the same donor, excluding a bias by proliferation of a certain 2S albumin-binding B-cells. In turn, IGHV4 genes accounted for a larger part of incorporated VH-genes in tolerant (21%) donors than in allergic ones (7%) (Table 2). Overall, VH-family gene usage differs between allergic and tolerant patients sensitized to Ara h2/6, supporting the hypothesis of differences in allergen specific antibody repertoires between allergic and tolerant patients.