Positive selection from newly formed to marginal zone B cells depends on the rate of clonal production, CD19, and btk.

Using immunoglobulin heavy chain transgenic mice, we show that B cell clones reaching the long-lived pool are heterogeneous: some are enriched in the CD21(high) compartment (mostly marginal zone [MZ]), others reside primarily in the follicles (FO). Altering the composition of the B cell receptor through N region additions decreases the rate of clonal production and the MZ enrichment. This process can be recapitulated by purified CD21(low) B cells and is due to a preferential clonal survival that requires a functional btk tyrosine kinase. We also show that generation of the MZ population is dependent on CD19. These findings suggest that the MZ B cell repertoire is positively selected and have functional implications for antigenic responses effected by B cells from this microenvironment.