Normal pre-B cells express a receptor complex of mu heavy chains and surrogate light-chain proteins.

Abstract

Early experimental observations contrary to this concept of pre-B-cell development (6-10) have received unexpected support from the recent discovery of A5 and Vpre-B genes in mice (11-13) and their counterparts in humans (13-16). The Vpre-B gene has significant homology to the LC variable region (VL) genes but lacks recombination signal sequences (12). The A5 gene encodes a protein containing LC joining region (JL)-and A-chain constant region (CA)-like sequences (13,15,16). These A-locus genes are also unusual in that they do not require rearrangement for their expression, which occurs exclusively in pre-B cells (11)(12)(13)(14)(15)(16). The Vpre-B and A5 gene products can be identified together with ,t chains on murine (17) and human (13, 15, 18) pre-B-cell lines. The A5 product of =22 kDa is covalently attached to membranebound ,L chains, while the 18-kDa Vpre-B protein is noncovalently bound (13,17,18

Immunoglobulin gamma 2b transgenes inhibit heavy chain gene rearrangement, but cannot promote B cell development.

“…Before the production of light chain, the heavy chain is expressed in a pre-B cell receptor complex with the surrogate light chains A5 and VpreB that is also capable of signal transduction (39)(40)(41)(42). The importance of this receptor is inferred by the block in early B cell development observed in either P.mem or A5 knockout mice (2, 29) .…”

Ordering human CD34+CD10−CD19+pre/pro-B-cell and CD19−common lymphoid progenitor stages in two pro-B-cell development pathways

“…Pro-B cells, which retain CD34 and CD10 expression but also express CD19 (CD34 + CD10 + CD19 + ), constitute the first Pax-5 + committed B-lineage stage, which is followed by pre-B (CD34 − CD10 + CD19 + ) cells that have ceased expression of CD34 and now express the surface μH-VpreB-λ5/CD79 surrogate Ig receptor complex (1)(2)(3)(4)(5)(13)(14)(15). Development of the latter CD34 − pre-B cells and their B-cell and Ig-secreting plasma cell progeny can be reconstituted after coculture of purified CD34 + Lineage − (Lin − ) progenitors with bone marrow (BM) stroma lines (e.g., S17) (15)(16)(17)(18).…”

“…B1 and B2 cells | CD19, a Pax5 reporter stepwise acquisition | layered Blymphocyte lineages | single-cell gene and protein expression profiles | umbilical cord blood W hereas models of human B-lineage development propose a single hierarchical development pathway from CD34 + stem cells (SCs) to B cells (1)(2)(3)(4)(5)(6), studies to track the order of emergence of B-cell differentiation stages in the mouse have documented distinct B-cell lineages, termed B-1 and B-2 (7-9).…”

Transgenic Human λ5 Rescues the Murine λ5 Nullizygous Phenotype

“…The expression of a functional hu 5 gene is crucial for B lymphopoiesis as a patient with a null mutation of the hu 5 gene has a severe B cell deficit and aggamaglobulinema due to a complete block at the pro-B to pre-B cell stage (40). Similar to the m 5 gene, the hu 5 gene is expressed at the pro-B and pre-B cell stages (16,37,(41)(42)(43)(44)(45). To begin to identify potential cis-regulatory elements important for the early B lineage expression of the hu 5 gene, our laboratory analyzed the hu 5 gene locus for sites of nucleosome reconfigurations using DNase I hypersensitivity mapping (45).…”

“…The exact function of the SLC, including 5, is unknown, but the pre-BCR apparently plays a critical role in B lineage differentiation as targeted disruption of the m 5 gene blocks B lymphocyte development at the transition between the pro-B cell and large pre-B cell stages and drastically reduces the number of mature B lymphocytes in the periphery (10 -12). It has been hypothesized that the pre-BCR provides a signal for B lineage differentiation from the pro-B to pre-B cell stages (10,(13)(14)(15)(16)(17) and allelic exclusion at the early or large pre-B cell stage (18,19). Pre-B cell signaling has also been implicated for cell survival/proliferation (12) and to screen for functional chains (20,21) and thus influence the V H repertoire (20 -23).…”