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T15-Idiotype-Negative B Cells Dominate the Phosphocholine Binding Cells in the Preimmune Repertoire of T15i Knockin Mice

Lina Hu^1,2,*, Louis J. Rezanka^1,*, Qing-Sheng Mi, Ana Lustig^*, Dennis D. Taub^*, Dan L. Longo^* and James J. Kenny^*

^* Laboratory of Immunology, Gerontology Research Center, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224; and Autoimmune and Diabetes Group, J. P. Robarts Research Institute, London, Ontario, Canada

T15i knockin (KI) mice express a H chain that is encoded by a rearranged T15 VDJ transgene which has been inserted into the J_H region of chromosome 12. This T15H chain combines with a 22–33 L chain to produce a T15-Id⁺ Ab having specificity for phosphocholine (PC). Inasmuch as T15-Id⁺ Abs dominate the primary immune response to PC in normal mice, it was surprising to find that 80% of the PC-dextran-binding B cells in unimmunized homozygous T15i KI mice were T15-Id^-. Analysis of L chains expressed in these T15-Id^-, PC-specific B cells revealed that two L chains, 8–28 and 19–15, were expressed in this population. The V region of these L chains was recombined to J5, which is typical of L chains present in PC-specific Abs. When T15i KI mice were immunized with PC Ag, T15-Id⁺ B cells expanded 6-fold and differentiated into Ab-secreting cells. There was no indication that the T15-Id^- B cells either proliferated or differentiated into Ab-secreting cells following immunization. Thus, T15-Id^- B cells dominate the PC-binding population, but they fail to compete with T15-Id⁺ B cells during a functional immune response. Structural analysis of T15H:8–28L and T15H:19–15L Abs revealed L chain differences from the 22–33 L chain which could account for the lower affinity and/or avidity of these Abs for PC or PC carrier compared with the T15-Id⁺ T15H:22–33L Ab.

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