Interrelating B Cell Subpopulations and Environmental Regulation with the Expression of Three Tiers of Repertoire Diversity

Abstract

The B cell repertoire consists of three tiers of clonotype diversity. One tier, which is the product of H chain V region rearrangements in the absence of N additions, is of limited diversity (< 10⁸ clonotypes) so that clonotypes of this tier would be expected to recur within and among B cells of individuals of an inbred strain. These clonotypes, therefore, could be subjected to, and conserved by, evolutionary selective pressures such as those imposed by ubiquitous bacterial pathogens. The second tier of clonotypes is created by H chain V region rearrangements that include N additions, and is, therefore, exceedingly diverse. Clonotypes of this tier would be unlikely to recur; however, by providing maximal diversity they would ensure protection against a wide spectrum of pathogens. The third tier of diversity is that which is generated by the superimposition of somatic mutations on clonotypes of the other two tiers. This tier of clonotypes is reflective of the refinement of specificities that are destined for expression in memory B cells.

B cells exist as three distinct subpopulations, Ly-1 B cells, conventional primary B cells and memory B cells. These subpopulations differ functionally, developmentally, and by the extent to which they are impacted by immunoregulatory processes. Furthermore, B cells of these subpopulations differentially express the three tiers of clonotype diversity.

Key Words:

• repertoire diversity
• predetermined permutation
• conventional B cells
• Ly-1 B cells
• memory B cells
• neonatal development
• evolutionary selection
• tolerance
• anti-idiotypic regulation
• recombination