B cell immune repertoire diversifies in a predictable temporal order in vitro.

The appearance of functional, antigen-specific B cells was studied in an in vitro fetal organ culture system in the absence of environmental influences associated with circulation and cell migration. In this way the B cell diversification process could be analyzed when genetic influences were dominating. By using this system in combination with the splenic focus assay, the frequency of developing B cells responsive to a number of hapten probes was measured. The results indicate that B cell diversification in vitro, in the apparent absence of many environmental influences, results in the appearance of antigen-responsive B cells in a predictable, temporal order. The results suggest that the acquisition of the expressed repertoire to a large extent is genetically controlled.