THE ROLE OF CELLULAR COMPETITION IN B-CELL SURVIVAL AND SELECTION OF B-CELL REPERTOIRES

We studied the competitive repopulation by different B cells of irradiated mice reconstituted with bone marrow from either congenic or Ig-transgenic (TG) mice mixed at different ratios. We found that after reconstitution, the number of B cells recovered in the different chimeras is similar and independent of the ratio of injected cells. In chimeras hosting TG and non-TG cells, the relative representation of the donor cell lineages diverges from the ratios present in the inoculum, i.e. at the periphery, non-TG cells are preferentially selected. Selection of non-TG cells only occurs when population growth plateaus, i.e. when resources become limiting and competition starts to operate. Selection of non-TG cells depends on surface Ig expression, and they are selected because they have a longer survival. Finally, the life-expectancy of the same B cell population differs depending upon the second population present. The present results show that the life-span and the population size of each B cell clone can be altered (interfered with) by the presence of a second cell population, demonstrating the existence of cellular competition among B cells. Our findings establish the role of cellular competition in the selection of B cell repertoires and the existence of a hierarchy of B cell selection in the absence of antigenic stimulation. The implications of cellular competition on our understanding of the immune system are discussed.