Immune Netw.  2015 Jun;15(3):161-166. 10.4110/in.2015.15.3.161.

Early Growth Response-1 Plays a Non-redundant Role in the Differentiation of B Cells into Plasma Cells

• Oh YK
• Jang E
• Paik DJ
• Youn J

• KMID: 2168042
• DOI: http://doi.org/10.4110/in.2015.15.3.161

Abstract

Early growth response (Egr)-1 is a Cys2-His2-type zincfinger transcription factor. It has been shown to induce survival and proliferation of immature and mature B cells, respectively, but its role in the differentiation of B cells into plasma cells remains unclear. To examine the effects of Egr-1 deficiency on the activation of B cells, naive B cells from Egr1-/- mice and their wild-type (WT) littermates were activated to proliferate and differentiate, and then assayed by FACS. Proportions of cells undergoing proliferation and apoptosis did not differ between Egr1-/- and WT mice. However, Egr1-/- B cells gave rise to fewer plasma cells than WT B cells. Consistently, Egr1-/- mice produced significantly lower titer of antigen-specific IgG than their WT littermates upon immunization. Our results demonstrate that Egr-1 participates in the differentiation program of B cells into plasma cells, while it is dispensable for the proliferation and survival of mature B cells.

Keyword

Egr1; B cells; Plasma cells; Differentiation; Antibody

MeSH Terms

Animals
Apoptosis
B-Lymphocytes*
Immunization
Immunoglobulin G
Mice
Plasma Cells*
Transcription Factors
Immunoglobulin G
Transcription Factors

Figure

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  Figure 1 A selective lack of Egr-1 expression in Egr1-/- cells. Splenocytes from WT and Egr1-/- mice were treated with PMA and ionomycin (P/I) for 1 or 3 h, and assayed by semi-quantitative (A) and quantitative RT-PCR (B). Egr1 mRNA expression was normalized to that for β2m. Data are representative of three independent experiments.

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  Figure 2 Analysis of naive B, germinal center B, and CD4+ T cell populations in Egr1-/- mice. (A) Spleen cells from 12 week-old Egr1-/- mice and their WT littermates were stained for the presence of GL7, B220 and CD4, and analyzed by FACS. The dot plots show total B (B220+), CD4+ T, naive B (B220+GL7lo), and germinal center (GC) B cell (B220+GL7hi) populations with relevant percentages. Presented values are representative of six independent experiments. (B) The proportions (mean±SEM) of indicated cell compartments.

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  Figure 3 Responses of Egr1-/- B cells to polyclonal stimulants. Naive B cells sorted from spleens of WT and Egr-1-/- mice were stained with CFSE and stimulated with LPS/IL-4 (A) or anti-IgM/IL-4 (B). After 4 days, cell proliferation, apoptosis and plasma cell development were analyzed by FACS. The data presented are representative of results from more than three independent experiments. Values indicate the percentages of cells within indicated areas.

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  Figure 4 Reduced Ab production in Egr1-/- mice. WT and Egr1-/- mice were immunized with NP-KLH/alum, and serum was collected at 14 and 21 days after immunization. Titers of NP-specific IgG were detetmined by ELISA. Values represent the mean±SEM arbitrary unit (AU)/ml, pooled from three independent experiments (n=10~12 per group). p-values were determined using unpaired two-tailed Student's t-tests. ND, not detected.

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