Natural antibodies contribute to tissue homeostasis and protect against infections. They are secreted constitutively without external antigenic stimulation. The differentiation state and regulatory pathways that enable continuous natural antibody production by B-1 cells, the main cellular source in mice, remain incompletely understood. Here we demonstrate that natural IgM-secreting B-1 cells in the spleen and bone marrow are heterogeneous, consisting of (a) terminally differentiated B-1–derived plasma cells expressing the transcriptional regulator of differentiation, Blimp-1, (b) Blimp-1⁺, and (c) Blimp-1^neg phenotypic B-1 cells. Blimp-1^neg IgM-secreting B-1 cells are not simply intermediates of cellular differentiation. Instead, they secrete similar amounts of IgM in wild-type and Blimp-1–deficient (PRDM-1^ΔEx1A) mice. Blimp-1^neg B-1 cells are also a major source of IgG3. Consequently, deletion of Blimp-1 changes neither serum IgG3 levels nor the amount of IgG3 secreted per cell. Thus, the pool of natural antibody-secreting B-1 cells is heterogeneous and contains a distinct subset of cells that do not use Blimp-1 for initiation or maximal antibody secretion.

天然抗体有助于组织动态平衡并防止感染。它们在没有外部抗原刺激的情况下组成性分泌。B-1细胞（小鼠中的主要细胞来源）能够连续产生天然抗体的分化状态和调控途径仍未完全了解。在这里，我们证明脾脏和骨髓中天然分泌IgM的B-1细胞是异质的，由（a）表达分化的转录调节因子Blimp-1的终末分化B-1衍生浆细胞组成，（b）Blimp -1 ⁺和（c）Blimp-1 ^neg表型B-1细胞。Blimp-1 ^neg分泌IgM的B-1细胞不仅仅是细胞分化的中间产物。相反，他们在野生型和Blimp-1缺陷型（^PRDM - ^1ΔEx1A）小鼠中分泌相似量的IgM 。Blimp-1 ^neg B-1细胞也是IgG3的主要来源。因此，Blimp-1的缺失既不会改变血清IgG3水平，也不会改变每个细胞分泌的IgG3量。因此，天然的分泌抗体的B-1细胞库是异质的，并且包含不使用Blimp-1进行初始或最大抗体分泌的独特细胞子集。