Avian B cell precursors: Surface immunoglobulin expression is an early, possibly bursa‐independent event

Abstract

The avian bursa of Fabricius contains about 1 X 10(4) discrete follicles, each of which is colonized by a small number of lymphoid progenitor cells during embryonic life. We have previously shown (J.R.L. Pink et al., Eur. J. Immunol. 1985. 15:617) that all, or almost all B cell progenitors in the bursae of 4-day-old chicks express cell surface IgM. In this report, we have analyzed the distribution of cell surface (s)IgM-1 allotypes within individual follicles of (M-1a/M-1b) allotype heterozygous birds. Although the majority of follicles contained a mixture of sIgM-1a+ and sIgM-1b+ cells, a significant proportion of isolated follicles contained exclusively sIgM-1a+ or sIgM-1b+ cells. Statistical analysis of the frequency of such "M-1a" and "M-1b" follicles demonstrated that the sIg+ B cells in the bursae of 4-8-week-old birds are derived from 2-4 allotypically committed precursor cells per follicle. Since we have previously shown that each bursal follicle is colonized by 2-5 pre-bursal stem cells, these cells must be committed to the eventual expression of one or other allotypic haplotype before they have undergone extensive proliferation within the bursa. In addition, we show that almost all B progenitor cells from the bursae of chicks which had been allotype suppressed as embryos were committed to synthesis of the nonsuppressed allotype, showing that this commitment was essentially complete at the time of suppression (i.e. before 19 days of incubation). Finally the bone marrow of 16-day embryos was used to reconstitute the bursal lymphocytes of cyclophosphamide-treated host embryos. Reconstitution was inhibited by anti-Ig antiserum indicating that most 16-day embryonic BM-derived bursal cell precursors also express sIgM. These results raise the possibility that expression of sIgM may be controlled by a "biological clock" rather than by any inductive capacity of the bursal microenvironment. Furthermore, these results provide further evidence that in normal birds a self-renewing sIg+ B cell population in the hatched chicken is the sole source of B cells in the adult.

Perinatal Deletion of B Cells Expressing Surface Ig Molecules That Lack V(D)J-Encoded Determinants in the Bursa of Fabricius Is Not Due to Intrafollicular Competition

“…However, the frequency of bursal follicles that uniquely contained ϩ L Ϫ precursors was typically about 2%, indicating that the majority of ϩ L Ϫ bursal cells develop in follicles containing both ϩ L ϩ and ϩ L Ϫ cells. This is consistent with several reports demonstrating that a limited number of B cell precursors (between two and five) productively colonize each bursal follicle during embryogenesis and that there is no interfollicular trafficking of lymphoid cells within the bursa (10,21,22). Indeed in the case of a bursa containing 25% ϩ L Ϫ cells, in which each bursal follicle is colonized by three precursors, one would expect about 1.5% of follicles to have been colonized by three ϩ L Ϫ precursors.…”

“…Several experimental approaches have demonstrated that the B cells in each follicle are derived from a limited number (two to five) of sIg ϩ precursors and, further, that there is no traffic of B-lineage cells from one follicle to another (10,20,21). As a consequence, the increase in bursal cellularity observed after about embryonic day 15, when most immigration of B cell precursors to the bursa has ended, represents the consequences of B cell division within the bursa.…”

Cell Cycle Arrest and Apoptosis Induced by Notch1 in B Cells

“…34). The bursa is composed of about 10 4 follicles, each of which is colonized by a few B cell precursors expressing surface immunoglobulin (Ig) M at 8 -14 embryonic day (35)(36)(37)(38). The precursors proliferate enormously, and their numbers finally reach to 2-5 ϫ 10 5 /follicle.…”

Development of B cells expressing surface immunoglobulin molecules that lack V(D)J-encoded determinants in the avian embryo bursa of Fabricius

“…The bursa is colonized by a single wave of B cell precursors during embryogenesis starting at about embryonic day 8 (E8) and lasting about a week (11). Within the bursa, B cell precursors first are observed in the mesenchymal tissue, and 20,000-40,000 precursors subsequently migrate across the bursal epithelial basement membrane and begin to proliferate in oligoclonal clusters or epithelial buds from which the discrete follicles of the mature bursa are derived (12,13).…”

“…Although Ig gene rearrangement is not intrinsically biased toward productive rearrangement, only those B cells that have undergone productive rearrangement are selected within the bursa (15). Because there is no detectable clonal expansion of B cell precursors in bursal follicles before the expression of sIg (13), transit across the basement membrane and subsequent precursor expansion in epithelial buds require sIg expression and represent a critical checkpoint in B lymphopoiesis.…”