ZBTB38 is dispensable for antibody responses.

ZBTB38 is dispensable for antibody responses.
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ZBTB38 对于抗体反应来说是可有可无的。

DOI:
10.1371/journal.pone.0235183
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发表时间:
2020
期刊:
影响因子:
3.7
通讯作者:
Bhattacharya D
Bhattacharya D
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Wong R;Bhattacharya D

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BTB-ZF转录因子家族的成员,如BCL-6、ZBTB20和ZBTB32,调节抗原特异性B细胞分化、浆细胞寿命和抗体产生的持续时间。我们发现ZBTB38是BTB-ZF家族的另一个成员,在CpG基元上结合甲基化DNA,在生发中心B细胞和浆细胞中高度表达。为了确定ZBTB38在B细胞应答中的功能作用,我们制造了条件性缺乏该转录因子的小鼠。缺乏ZBTB38的生发中心B细胞相对于野生型和杂合的窝伴对照,很少有基因失调。因此,造血特异性缺失Zbtb38的小鼠在半抗原蛋白偶联物免疫后表现出正常的生发中心B细胞数量和抗体反应。这些动物的记忆B细胞在二次回忆反应中功能正常。尽管ZBTB38在造血干细胞中表达,但在突变小鼠中,祖细胞和成熟骨髓和淋巴细胞谱系也以正常数量存在。这些数据表明ZBTB38在造血和抗体应答中是不可或缺的。这些条件敲除小鼠可能有助于确定ZBTB38在其他细胞类型和环境中的功能重要性。
Members of the broad complex, tram track, bric-a-brac and zinc finger (BTB-ZF) family of transcription factors, such as BCL-6, ZBTB20, and ZBTB32, regulate antigen-specific B cell differentiation, plasma cell longevity, and the duration of antibody production. We found that ZBTB38, a different member of the BTB-ZF family that binds methylated DNA at CpG motifs, is highly expressed by germinal center B cells and plasma cells. To define the functional role of ZBTB38 in B cell responses, we generated mice conditionally deficient in this transcription factor. Germinal center B cells lacking ZBTB38 dysregulated very few genes relative to wild-type and heterozygous littermate controls. Accordingly, mice with hematopoietic-specific deletion of Zbtb38 showed normal germinal center B cell numbers and antibody responses following immunization with hapten-protein conjugates. Memory B cells from these animals functioned normally in secondary recall responses. Despite expression of ZBTB38 in hematopoietic stem cells, progenitors and mature myeloid and lymphoid lineages were also present in normal numbers in mutant mice. These data demonstrate that ZBTB38 is dispensable for hematopoiesis and antibody responses. These conditional knockout mice may instead be useful in defining the functional importance of ZBTB38 in other cell types and contexts.
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