H1N1 reactive mAbs isolated from infected patients (1000, EM, 70, 1009) were assayed for binding to annual H1N1 influenza strain whole virus. The minimum detectable concentration is defined as two standard deviations above the mean binding of 48 randomly chosen naive B cell antibodies ( Fig. S1 A) . Bars are color coded to approximate levels of crossreactivity to the annual vaccine (circulating) strains of recent years. Panels A and B use the same color scheme. Each value is representative of at least two replicate ELISAs repeated until a single consistent minimum concentration was established. The center numeral equals total antibodies. (C) Analysis of the variable gene sequences from plasmablasts of the four pandemic H1N1-infected patients indicated that 16.5% of the pandemic H1N1-induced plasmablasts were clonally related (shared identical VH and JH genes and CDR3 junctions). (D) The average number of somatic hypermutations in the pandemic H1N1 patient plasmablast variable region genes compared with primary IgG plasmablast responses to vaccinia (small pox) or the anthrax vaccine, or after at least 4 boosters with the anthrax vaccine. To account for the obvious outlier in the pandemic H1N1 group (patient-EM), median values are indicated by the bar. Student's t tests excluding the outlier indicated a p-value of <0.04 for the remaining five pandemic H1N1 samples compared with the IgG memory and germinal center (GC) cells or the primary IgG plasmablast responses (0.2 with EM included) and a p-value of <0.0001 against the IgM populations. Notably, besides patient EM, each individual set of VH genes averaged significantly more mutations than the IgG memory and GC or the primary responses ( Fig. S3 A) . Each point represents one individual donor and is averaged from 25-75 sequences, except for the primary response to anthrax from which only 10 VH genes could be cloned from single cells because of the highly limited response. Mutations accumulated per individual sequence are depicted in Fig. S3 . Detailed sequence characteristics are provided in Tables S1-S3. The naive, IgG and IgM GC and memory populations are derived from historical data (Zheng et al., 2004 (Zheng et al., , 2005 Koelsch et al., 2007; Wrammert et al., 2008) .