The ability of B cells to respond to an almost infinite universe of antigens relies on the extreme variability of the immunoglobulins (Ig). Ig genes are assembled by stepwise by recombinations of the available Variable (V), Diversity (D) and Joining (J) gene segments, VD and DJ junctional diversity and somatic hypermutations within the CDR regions of the antigen binding site of the antibodies. Through iterative positive and negative selection only B cell clones with improved antigen binding affinity survive, resulting in a repertoire of cells with highly specific B cell receptors. The analysis of these receptors is complicated by their excessively large number, exceeding 10¹² different B cells in humans and 10⁸ in mice.Advances in high-throughput DNA sequencing technology have made it possible to study the complete repertoire of antigen-specific B cell receptors at unprecedented depth.Since the B cell repertoire is shaped by the antigens encountered, the approach has the potential to retrospectively analyze past immune responses and potentially reconstruct past antigenic challenges. We have analyzed the B cell repertoire of mice, rats and humans to identify antigen specific signatures against viruses, bacteria and small molecular-weight haptens. To study the dynamic of the B cell repertoire and to identify specific immunoglobulin signatures against measles virus (MV), rats with a human Ig heavy chain repertoire (OmniRats) were immunized with a variety of measles antigens and >200 specific (human) hybridomas were generated. The humanized rats generated a normal human response utilizing essentially all heavy chain V, D, J genes and recombination. About 1 Mio CDR3 sequences were obtained from the rats’ lymph nodes, the hybridoma library and the hybridoma clones of which about 2800 were unique. 2.5 Mio sequences were obtained from 4 naïve animals 30.000 of which were unique. When the sequences of MV immunized rats and naïve rats werecompiled and sorted according to 80% aminoacid similarity 5809 clusters of 1 to 118 sequences emerged. MV specific sequences from the hybridoma clones were mainly found in the clusters that resulted from B cell proliferation and mutational/junctional diversification. The MV specificity of the clusters was further confirmed by showing that the sequence clusters of naïve animals or immunized with other antigens (tetanus toxoid, benzo[a]pyrene) were segregated from the measles clusters and showed little overlap with these. The MV specific sequences were also compared with sequences obtained from measles patients and individuals vaccinated with MV containing vaccine. The conclusion of our studies is that antigen induce specific immunoglobulin sequences that can be recognized on the basis of proliferation and diversity characteristics and that these sequence clusters correspond to complex signatures that eventually could be exploited to reproduce the immunological history of the host.