EXPRESSION OF LAMBDA-GENES AND KAPPA-GENES CAN OCCUR IN ALL B-CELLS AND IS INITIATED AROUND THE SAME PRE-B-CELL DEVELOPMENTAL STAGE

Transgenic mice that carry a gamma 2 transgene under the control of the V gamma 2 promoter and the E gamma 2-4 enhancer (gamma 2E gamma mice) are described. A high proportion of B cells in the spleen and the bone marrow express the gamma transgene on the cell membrane. gamma 2 protein is synthesized by all gamma 2E gamma-derived spleen B-cell hybridomas that have retained the transgene, suggesting that all B cells have the ability to express gamma genes. Feedback inhibition of endogenous K-gene rearrangement is significant, but not complete. The results are similar to those with transgenic mice expressing the same gamma 2 transgene under the control of the heavy-chain enhancer (gamma 2EH mice). Although the gamma 2EH transgene is expressed before the gamma 2E gamma transgene, feedback inhibition seems to occur at about the same stage of B-cell development, regardless of the timing of expression of the gamma transgenes. Apparently, feedback is not necessarily coincident with the assembly of a heavy-chain/light-chain complex in pre-B cells. Expression of gamma in the normal fetal liver coincides with the expression of K; thus, it appears that gamma-gene transcription is not delayed. The differential rearrangement of K and gamma genes is discussed in the light of these findings.