Seidel Anne-Marie, Kauffold Johannes, Protschka Martina, Baums Christoph G, Alber Gottfried, Eschke Maria
Institute of Immunology, Centre for Infectious Diseases, Faculty of Veterinary Medicine, Centre for Biotechnology and Biomedicine, Leipzig University, Leipzig, Germany.
Clinic for Ruminants and Swine, Faculty of Veterinary Medicine, Leipzig University, Leipzig, Germany.
Front Immunol. 2024 Nov 18;15:1495359. doi: 10.3389/fimmu.2024.1495359. eCollection 2024.
serotype () 2 is an important bacterial pathogen in piglet nurseries and an emerging zoonotic agent without effective vaccines available. Immunoglobulin (Ig)M plays an essential role in host defense against . In mice, non-conventional B-1 cells are a major source of protective IgM against encapsulated bacterial pathogens, such as . Two IgMCD21 B-1-like cell subpopulations, distinguishable by CD11R1 expression, were described in pigs, but their properties and functions are poorly understood. This study aimed at a first characterization of the porcine early IgM B cell response against 2.
We analyzed the same healthy pigs, naturally colonized by different serotypes, including 2, at four and eight weeks of age serologically and determined the frequency of different peripheral B cell subpopulations by flow cytometry. Furthermore, we isolated conventional IgMCD21 B-2 cells as well as non-conventional B-1-like cell subpopulations from peripheral blood of eight-weeks-old pigs to evaluate their potential of IgM secretion in response to innate and adaptive stimuli .
Between the fourth and eighth week of life, a characteristic increase of 2-binding serum IgM antibodies, restricting bacterial growth, was observed. Moreover, we show for the first time that the significant increase of anti- serum IgM is associated with a relative increase of peripheral non-conventional IgMCD21 B-1-like cells , particularly of the IgMCD21 CD11R1 subpopulation. Noteworthy, sorted IgMCD21 CD11R1 B-1-like cells from eight-weeks-old pigs spontaneously secreted IgM . In addition, both non-conventional IgMCD21 B cell subpopulations, in contrast to conventional IgMCD21 B-2 cells, produced anti- IgM upon toll-like receptor (TLR) stimulation underlining their innate-like characteristics. We furthermore observed that both B-1-like subpopulations secrete 2-binding IgM upon stimulation with T cell-associated factors with highest amounts in IgMCD21CD11R1 B-1-like cells even exceeding anti- IgM levels produced by B-2 cells.
Porcine non-conventional B-1-like cells are a potent source of -binding IgM indicating a role in immunity during a critical phase of piglet rearing.
血清型2是仔猪保育舍中的一种重要细菌病原体,也是一种新兴的人畜共患病原体,目前尚无有效的疫苗。免疫球蛋白(Ig)M在宿主抵御血清型2的过程中发挥着重要作用。在小鼠中,非常规B-1细胞是针对包膜细菌病原体(如血清型2)产生保护性IgM的主要来源。猪体内存在两种可通过CD11R1表达区分的IgM⁺CD21⁻B-1样细胞亚群,但其特性和功能尚不清楚。本研究旨在首次对猪针对血清型2的早期IgM B细胞反应进行表征。
我们对相同的健康猪进行了分析,这些猪在4周龄和8周龄时自然定殖有不同血清型,包括血清型2,通过血清学方法进行检测,并通过流式细胞术确定不同外周血B细胞亚群的频率。此外,我们从8周龄猪的外周血中分离出常规IgM⁺CD21⁻B-2细胞以及非常规B-1样细胞亚群,以评估它们在受到先天和适应性刺激时分泌IgM的潜力。
在出生后的第4周和第8周之间,观察到限制细菌生长的血清型2结合血清IgM抗体有特征性增加。此外,我们首次表明,抗血清型2血清IgM的显著增加与外周非常规IgM⁺CD21⁻B-1样细胞的相对增加有关,特别是IgM⁺CD21⁻CD11R1亚群。值得注意的是,从8周龄猪中分选的IgM⁺CD21⁻CD11R1 B-1样细胞自发分泌IgM。此外,与常规IgM⁺CD21⁻B-2细胞相比,两种非常规IgM⁺CD21⁻B细胞亚群在Toll样受体(TLR)刺激下均产生抗血清型2 IgM,突出了它们类似先天的特征。我们还观察到,两种B-1样亚群在受到T细胞相关因子刺激后均分泌血清型2结合IgM,其中IgM⁺CD21⁻CD11R1 B-1样细胞中的分泌量最高,甚至超过了B-2细胞产生的抗血清型2 IgM水平。
猪的非常规B-1样细胞是血清型2结合IgM的有力来源,表明其在仔猪饲养关键阶段的免疫中发挥作用。