CHARACTERISTICS OF HUMAN-ANTIBODY REPERTOIRES FOLLOWING ACTIVE IMMUNE-RESPONSES IN-VIVO

Possibilities to develop human monoclonal antibody specificities have recently been much facilitated by improvements of human hybridoma tech nology but even more so by the emerging phage-display technique. Howev er, until recently very little has been known about the characteristic s al the molecular level of the induced, T cell-dependent human antibo dy response, frequently targeted by these techniques. Rather, the majo r part of available sequence information has been related to tumor-der ived or autoreactive antibodies. We have now investigated high affinit y, monospecific, human antibody repertoires as developed by hybridoma technology. The VH region gene usage among such in vivo-induced repert oires is in only some respects similar to that found in the total B ce ll population. A limited number of heavy-chain variable segment loci a ccount for the majority of all induced antibodies. A particular VH gen e locus (4-34) frequently employed by peripheral B cells and associate d with autoreactive antibodies was rarely used by the induced repertoi re. Furthermore, in particular antigen systems, V region usage differs from the total available repertoire, and heavy-chain CDR3 is generall y longer among antibodies induced against foreign protein antigens tha n in the average B cell population. Light-chain gene usage is often re stricted to just a few dominant genes frequently found among B cells i n general. In comparison, variable regions derived by phage-display te chnology in some antigen systems display even longer heavy-chain CDR3 than hybridoma-derived antibodies. This technique also appears to sele ct a different set of germline genes preferentially (both with respect to VH and JH) as compared to hybridoma technology. In summary, the T cell-dependent antibody response against foreign antigens appears to d iffer from the average circulating B cell in several ways, and thus do es not seem to represent a random selection of the available repertoir e. Copyright (C) 1996 Elsevier Science Ltd.