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

Abstract

T15i knockin (KI) mice express a H chain that is encoded by a rearranged T15 VDJ transgene which has been inserted into the JH region of chromosome 12. This T15H chain combines with a κ22–33 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, κ8–28 and κ19–15, were expressed in this population. The Vκ region of these L chains was recombined to Jκ5, 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:κ8–28L and T15H:κ19–15L Abs revealed L chain differences from the κ22–33 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:κ22–33L Ab.