Kramer D R, Cebra J J
Department of Biology, University of Pennsylvania, Philadelphia 19104.
J Immunol. 1995 Mar 1;154(5):2051-62.
We have examined the role of passively transferred maternal Abs in the ontogeny of "natural" mucosal IgA responses before weaning of suckling mice by comparing the immune status of gut-associated lymphoid tissue (GALT) (Peyer's patches, mesenteric lymph nodes, and lamina propria) in 7- to 25-day-old F1 severe combined immunodeficient (scid)/+ mice generated through reciprocal crosses of C.B17 scid/scid and normal congenic (+/+) adult mice. We have also examined the ability of prenatal vs postnatal transfer of maternal immunity to forestall the development of natural neonatal mucosal IgA responses by swapping litters of F1 scid/+ pups at birth between +/+ and scid/scid mothers. Our results demonstrate that F1 scid/+ pups born to or nursed by scid/scid mothers undergo an accelerated development of natural IgA responses that include germinal center reactions in both Peyer's patches and mesenteric lymph nodes. These early IgA responses are evident as: 1) increased frequencies of IgA-producing GALT organ cultures; 2) increased mean IgA output by GALT organ cultures; 3) increased frequencies (> 1 log) of IgA-secreting cells from GALT detected by ELISPOT at 16 days of age; and 4) germinal center development by 17 days of age detected by in vivo bromodeoxyuridine incorporation. Finally, FACS analyses of enteric bacteria isolated from F1 scid/+ pups and stained for the presence of surface-bound mouse IgA demonstrate that the bacterial flora is a major target of both maternal secretory IgA and of the earliest IgA Abs produced in the neonatal GALT of pups deprived of maternal immunity.
我们通过比较7至25日龄的F1严重联合免疫缺陷(scid)/+小鼠肠道相关淋巴组织(GALT)(派尔集合淋巴结、肠系膜淋巴结和固有层)的免疫状态,研究了被动转移的母源抗体在哺乳小鼠断奶前“天然”黏膜IgA应答个体发育中的作用。这些F1严重联合免疫缺陷(scid)/+小鼠是通过C.B17 scid/scid和正常同基因(+/+)成年小鼠的正反交产生的。我们还通过在出生时在+/+和scid/scid母亲之间交换F1 scid/+幼崽的窝,研究了产前与产后母源免疫转移预防天然新生儿黏膜IgA应答发展的能力。我们的结果表明,由scid/scid母亲生育或哺乳的F1 scid/+幼崽天然IgA应答加速发展,包括派尔集合淋巴结和肠系膜淋巴结中的生发中心反应。这些早期IgA应答表现为:1)产生IgA的GALT器官培养物频率增加;2)GALT器官培养物的平均IgA产量增加;3)16日龄时通过ELISPOT检测到的来自GALT的IgA分泌细胞频率增加(>1个对数);4)通过体内溴脱氧尿苷掺入在17日龄时检测到生发中心发育。最后,对从F1 scid/+幼崽分离并染色以检测表面结合的小鼠IgA的肠道细菌进行流式细胞术分析表明,细菌菌群是母源分泌型IgA以及在缺乏母源免疫的幼崽新生儿GALT中产生的最早IgA抗体的主要靶标。