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International Immunology, Vol. 11, No. 7, 1157-1167, July 1999
© 1999 Japanese Society for Immunology

Molecular and cellular basis of the altered immune response against arsonate in irradiated A/J mice autologously reconstituted

Jamila Ismaïli1, Diane Razanajaona2, Annette Van Acker1, Christian Wuilmart1, Isabelle Mancini3, Ernst Heinen3, Oberdan Leo1, Serge Lebecque2, Jacques Urbain1 and Maryse Brait1

1 Université Libre de Bruxelles, Laboratory of Animal Physiology, rue des Chevaux 67, 1640 Rhode-Saint-Genèse, Belgium
2 Schering-Plough, Laboratory for Immunological Research, 27 chemin des Peupliers, BP11, 69571 Dardilly, France
3 Université de Liège, Unité d'Immunologie, rue des Pitteurs 20, 4020 Liège, Belgium

Correspondence to: P. J. Urbain

The humoral immune response to arsonate (Ars) in normal A/J mice is dominated in the late primary and particularly in the secondary response by a recurrent and dominant idiotype (CRIA) which is encoded by a single canonical combination of the variable gene segments: VHidcr11–DFL16.1–JH2 and V{kappa}10–J{kappa}1. Accumulation of somatic mutations within cells expressing this canonical combination or some less frequent Ig rearrangements results in the generation of

high-affinity antibodies. By contrast, in partially shielded and irradiated A/J mice (autologous reconstitution) immunized with Ars–keyhole limpet hemocyanin (KLH), both the dominance of the CRIA idiotype and the affinity maturation are lost, whereas the anti-Ars antibody titer is not affected. To understand these alterations, we have analyzed a collection of 27 different anti-Ars hybridomas from nine partially shielded and irradiated A/J mice that had been immunized twice with Ars–KLH. Sequence analysis of the productively rearranged heavy chain variable region genes from those hybridomas revealed that (i) the canonical V(D)J combination was rare, (ii) the pattern of V(D)J gene usage rather corresponded to a primary repertoire with multiple gene combinations and (iii) the frequency of somatic mutations was low when compared to a normal secondary response to Ars. In addition, immunohistological analysis has shown a delay of 2 weeks in the appearance of full blown splenic germinal centers in autoreconstituting mice, as compared to controls. Such a model could be useful to understand the immunological defects found in patients transplanted with bone marrow.

Keywords: bone marrow, idiotypes, lymphoid organization, memory, repertoire development

The first three authors contributed equally to this work

Transmitting editor: H. Bazin


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