The Formation and Selection of Cells Expressing PreB Cell Receptors and B Cell Receptors

Abstract

The repertoires of B cell receptor (Ig)-expressing B cells are generated during B cell development in a stepwise fashion (Tonegawa 1983). First, D_H segments are rearranged to J_H segments on the H chain locus at the transition from B220⁺CD19^- proB cells to B220⁺CD19⁺ckit⁺ preB-I cells. In most preB-I cells both H chain alleles are D_HJ_H-rearranged (Rolink et al. 1995). PreB-I cells, as proB cells, express the VpreB and λ₅ proteins of the surrogate L chain (Melchers et al. 1993) and the preB cell — and B cell — receptor-anchoring proteins Igα and Igβ (Reth 1994). Next, V_H segments are rearranged to D_HJ_H segments (Alt et al. 1984) at the transition from preB-I to preB-II cells (ten Boekel et al. 1995). Whenever this rearrangement occurs in-frame, a μH chain can be expressed. Productive V_HD_HJ_H- rearranged H chain alleles are found in large, cycling ckit^- CD25⁺ preB-II cells which, like all subsequent stages of B cell development, all express an H chain in their cytoplasm (Rolink et al. 1994). One fifth of all large preB-II cells express the μH chains as complexes with surrogate L chains as so-called preB cell receptors on their surface (Winkler et al. 1995). In these cells the L chain loci remain in germline configuration, and are not transcribed. The other portion of the large preB-II cells appears further progressed in development. They no longer express the preB cell receptor, in fact, they have the expression of the surrogate L chain genes downregulated, and begin to transcribe L chain loci (Grawunder et al. 1995). A small fraction of preB-II cells expressing μH chains in their cytoplasm continues to express ckit and surrogate L chain, but fails to express preB cell receptors on their surface. Their properties are described below.