Pre-B cell receptor expression is necessary for thymic stromal lymphopoietin responsiveness in the bone marrow but not in the liver environment - PubMed (original) (raw)

Pre-B cell receptor expression is necessary for thymic stromal lymphopoietin responsiveness in the bone marrow but not in the liver environment

Christian A J Vosshenrich et al. Proc Natl Acad Sci U S A. 2004.

Abstract

IL-7 and thymic stromal lymphopoietin (TSLP) are two major cytokines controlling murine B cell development. IL-7 has been studied extensively, but only recently has it become possible to unravel the role of TSLP in detail. We studied the biological activities of TSLP in B cell development at distinct ages in the mouse. On the one hand, TSLP is able to give rise to a measurable B1 cell compartment derived from fetal liver pro-B cells, although, as is the case for B2 cells, it does not play a prevalent role in the development of this subset. On the other hand, TSLP drives the proliferation of pro-B cells from the fetal and neonatal liver, but in the bone marrow environment, B cell precursors require pre-B cell receptor expression for TSLP responsiveness.

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Figures

Fig. 1.

Fig. 1.

TSLP supports the generation of B1 cells. (A) Number of B1 cells in the peritoneal cavity of control, γc°, IL-7Rα°, and γc°IL-7Rα° mice. The number of CD5+IgM+ cells found in the peritoneal cavity of the indicated mouse strains at 12 weeks of age is shown. n, number of mice analyzed; *, P < 0.01. (B) Fetal liver precursors from γc° and IL7Rα° mice have a 10- and 100-fold reduced capacity, respectively, to generate B1 cells upon transfer into alymphoid recipient mice. The number of B220+IgM+ cells found in the peritoneal cavity of Rag2°γc° mice 5 weeks after reconstitution with 105 sorted, day-15 FL precursors from donor mice of the indicated genotypes is shown. *, below detection limit.

Fig. 2.

Fig. 2.

TSLP and IL-7 drive the generation of IgM+ cells. Phenotypic analysis of BM-derived C57BL/6(Upper) and C57BL/6.IL-7° (Lower) pro-B cells from 1- to 2-week-old mice cultured for 7 days in the presence of NIH 3T3 feeder cells supplemented with IL-7 (Left) or TSLP (Right). Cultures with IL-7 typically yield 100 times, and TSLP cultures 30 times, more cells than at the start of the culture (not shown). Numbers indicate the percentage of IgM+ cells among CD19+ cells.

Fig. 3.

Fig. 3.

TSLP does not support the growth of BM B cell precursors from adult λ5° mice. Shown is a limiting dilution analysis of pro-B cells, isolated from adult BM of λ5° (▴), BALB/c.Rag2° (○), and BALB/c mice (•) in the presence of TSLP. The best-fit line crossing the origin is plotted. The dashed line intercepts the vertical axis at 37%. Data are representative of two experiments. No growth was observed in cultures not supplemented with either IL-7 or TSLP (not shown).

Fig. 4.

Fig. 4.

Expression of TSLP-R on BM precursor B cells from C57BL/6 and C57BL/6.Rag2° mice. BM cells from 8-week-old mice were stained for CD19, CD43, CD25, and TSLP-R. Shown are living (propidium iodide-negative) CD19+ BM cells from C57BL/6(Left) and C57BL/6.Rag2° (Right) mice. The expression of TSLP-R on pro-B cells (CD43+CD25–)(Upper) and pre-B cells (CD25+)(Lower) are shown as histograms. Gray shading indicates isotype control antibody.

Fig. 5.

Fig. 5.

The BM pro-B cell compartment in C57BL/6, C57BL/6.Rag2°, and H3 × Rag2° mice. BM cells from the indicated mice were stained for B220, CD43, HSA (30F1), and BP-1. Shown are the profiles of HSA versus BP-1 expression on gated B220+CD43+ BM cells. Cells of Hardy's fraction C (pro-B cells) and C′ (large pre-B cells) are boxed. Note the reduced level of expression of BP-1 on cells from fraction C′ in the BM of H3 × Rag2° mice.

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