Abstract: A system for continuous production and removal of a biological substance from a dispersed cell culture. The system comprises a reactor adapted to maintain the cell culture under incubating conditions and means for pumping limited volumes of the culture fluid from the reactor and through an external substance separation device adapted to extract the substance in a limited time on a continuous basis without collection of, or damage to, the dispersed cells. Less than 5% of the total culture fluid volume is outside the reactor (Volume outside or Vo) at any time and a given dispersed cell is outside the protective environment of the reactor for less than about two minutes, as expressed by the following relationship, ##EQU1## In preferred embodiments the external device comprises a plurality of substance-extracting, porous, hollow fibers through which the culture fluid, substance, and dispersed cells are continuously passed.

Abstract: Human-nonhuman heterohybridomas capable of expressing IgM type antibodies can be screened to select hybridomas expressing IgM antibodies comprising human J chain components. Method comprises contacting separate samples of IgM antibodies (or IgM J chain components) from a given cell line with anti-human J chain antibodies and anti-non-human J chain antibodies to determine which antibody complexes with the J chain component of the samples, thereby identifying and permitting the early selection of a heterohybridoma expressing IgM having a human J chain component.