T Cell Mediated Conversion of a Non-anti-La Reactive B cell to an Autoreactive anti-La B Cell by Somatic Hypermutation

Since the first description of the nuclear autoantigens in the late sixties and early seventies of the last century we and many other groups have tried with difficulty to establish monoclonal anti-bodies (mabs) against nuclear antigens including to the autoantigen La/SS-B. To date, only a few anti-La mabs have been derived by conventional hybridoma technology. However, these pre-viously described anti-La mabs are not bona fide autoantibodies as they recognize either human La specific- or cryptic or post-translationally modified epitopes which are not accessible on na-tive mouse La protein. Herein we present a series of novel murine anti-La mabs including truly autoreactive ones. These mabs were elicited from a human La transgenic animal through adop-tive transfer of T cells from non-transgenic mice immunized with human La antigen. Detailed epitope and paratope analyses experimentally confirm the hypothesis that somatic hypermuta-tions occurring during T cell dependent maturation can lead to autoreactivity to the nuclear au-toantigen La/SS-B.