GLOBAL ANALYSIS OF ANTIBODY REPERTOIRES .2. EVIDENCE FOR SPECIFICITY,SELF-SELECTION AND THE IMMUNOLOGICAL HOMUNCULUS OF ANTIBODIES IN NORMAL SERUM

The serum IgM repertoires of C57BL/6, DBA/2 and BALB/c mouse strains w ere analyzed using a recently developed global and quantitative assay that measures antibody reactivities to a very large number of antigens . A characteristic repertoire could be assigned to each strain. The di fferent repertoires could be successfully classified with multivariate statistics. Many common reactivities were also observed among the dif ferent strains, which allows the definition of a mouse-specific repert oire. Analysis of human sera support this notion. To investigate the i mpact of minor genetic differences on the serum IgM repertoire, the co ngenic strains B10.D2/oSn and B10.D2/nSn, which differ in the expressi on of the C5 component of complement, were analyzed. The two strains c ould be separated based on the reactivity profiles obtained. The analy sis of the results reveals that many antigenic proteins are not recogn ized at all by natural antibodies, while others are disproportionately reactive, the resulting patterns giving rise to what could be the def inition of an ''immunological homunculus''. The relevance of this type of analysis for clinical applications is discussed.