B-cell repertoire response to vaccine

caschramm · June 24, 2016, 6:27pm

Congrats to @jgalson on an interesting new paper!

ncbi.nlm.nih.gov

B-cell repertoire dynamics after sequential hepatitis B vaccination and evidence for cross-reactive B-cell activation.

JD Galson, J Trück, EA Clutterbuck, A Fowler, V Cerundolo, AJ Pollard, G Lunter and DF Kelly, Genome medicine, 2016 16 06

A diverse B-cell repertoire is essential for recognition and response to infectious and vaccine antigens. High-throughput sequencing of B-cell receptor (BCR) genes can now be used to study the B-cell repertoire at great depth and may shed more light on B-cell responses than conventional immunological methods. Here, we use high-throughput BCR sequencing to provide novel insight into B-cell dynamics following a primary course of hepatitis B vaccination.Nine vaccine-naïve participants were administered three doses of hepatitis B vaccine (months 0, 1, and 2 or 7). High-throughput Illumina sequencing of the total BCR repertoire was combined with targeted sequencing of sorted vaccine antigen-enriched B cells to analyze the longitudinal response of both the total and vaccine-specific repertoire after each vaccine. ELISpot was used to determine vaccine-specific cell numbers following each vaccine.Deconvoluting the vaccine-specific from total BCR repertoire showed that vaccine-specific sequence clusters comprised <0.1 % of total sequence clusters, and had certain stereotypic features. The vaccine-specific BCR sequence clusters were expanded after each of the three vaccine doses, despite no vaccine-specific B cells being detected by ELISpot after the first vaccine dose. These vaccine-specific BCR clusters detected after the first vaccine dose had distinct properties compared to those detected after subsequent doses; they were more mutated, present at low frequency even prior to vaccination, and appeared to be derived from more mature B cells.These results demonstrate the high-sensitivity of our vaccine-specific BCR analysis approach and suggest an alternative view of the B-cell response to novel antigens. In the response to the first vaccine dose, many vaccine-specific BCR clusters appeared to largely derive from previously activated cross-reactive B cells that have low affinity for the vaccine antigen, and subsequent doses were required to yield higher affinity B cells.

ematsen · June 26, 2016, 3:28am

My favorite part of this paper:

Enriching vaccine-specific clusters from the total repertoire. a The number of clusters from the total repertoire which were annotated by the four vaccine-enriched sequence datasets. b The percentage of abundant (>0.01 % of total repertoire) clusters at each visit that were characterized as vaccine-specific based on being annotated by at least two of the vaccine-enriched datasets. c Same as b but corrected for cluster size by considering the percentage of the repertoire comprising the vaccine-specific clusters. For b and c, mean values ± SEM are shown for all nine participants and p values were obtained from two-sided Mann–Whitney U tests. d Correlation (Spearman) between the percentage of abundant clusters characterized as vaccine-specific and PC numbers determined by ELISpot. Different colored points represent samples from the different participants. e Same as d but correlated with memory cell numbers determined by ELISpot. For d and e, samples where no cells were detected by ELISpot have been omitted

… we can make progress on understanding the (finite) set of ways to respond to a vaccine!