INDUCTION OF IgG BY LIPID A IN THE NEWBORN MOUSE

Kolb, Cornelia; Pauli, Raimund Di; Weiler, Eberhardt

doi:10.1084/jem.139.3.467

Cited by 11 publications

(7 citation statements)

References 16 publications

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“…Supposing the concentration of IgG2a b in normal serum to be between 0, 3, and 5 mg/ml, the test could detect 0 and 6-10 ~g IgG2ab/ml serum. Thus it is about fourfold less sensitive than the hemolysis assay used previously (4). However, since the present technique employs simple twofold dilution steps and readings of hemagglutination end points, using Takatsy microtiter equipment, it is considerably faster to perform.…”

Section: Assay For Igg Of B Allotypementioning

confidence: 94%

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Induction of IgG in young nude mice by lipid A or thymus grafts.

Kolb¹,

Pauli²,

Weiler³

1976

The Journal of Experimental Medicine

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Lipopolysaccharide (LPS) 1 from gram-negative bacteria, or the lipid A component isolated from LPS, have a potent stimulatory effect on B lymphocytes. In vitro, they induce both cell proliferation and IgM secretion (reviewed in references 1-3). In vivo, we have demonstrated a pronounced effect of lipid A administered to mice during the first few days of life: serum IgG rose rapidly to levels 10-to 50-fold higher than in untreated controls of the same age (4). By contrast, adult animals did not show a clear response to LPS or lipid A; the ability to respond to lipid A with IgG production is lost between 14 and 20 days of age (unpublished results). The dramatic response of new-born mice to lipid A is of interest in terms of the ontogenetic development of the Ig-producing limb of the immune system. We therefore studied the early Ig production in congenitally thymusless Cnude") mice and their response to lipid A and thymus grafts. The experiments to be presented were also prompted by reports showing that the limiting factor governing the capacity of young mice to give a humoral immune response could be the presence or maturity of thymus-dependent ~'helper" cells (5,6).A number of studies in vitro are concerned with the question whether or not T cells are participants in the stimulation of B cells by LPS or lipid A (7-9). The interpretation of the results is complicated by the finding that the nude mouse does possess some 0-positive cells (10), and that, in fact, LPS itself can induce precursor cells to express T-cell-specific antigens (11).In the design of the present experiments [as with those reported previously (4)] we had to take cognizance of the fact, that young animals bear high serum levels of maternal IgG. To measure selectively the autochthonous production of IgG by the young, we had to use allotypically heterozygous offspring, and assay only the Ig bearing the paternal allotype.The experiments show that lipid A can induce accelerated IgG production in young nudes, albeit not to the same degree as in normal young mice. IgG production was also dramatically stimulated by nearly congeneic thymus grafts; and the effects of lipid A and thymus grafts were additive and possibly cooperative. Materials and MethodsMice. The following mice were bred in our laboratory: BALB/c-AnNIcr; BALB/c-nu, a backcross-line developed in Konstanz by B. M. Kindred, which carries the nude (athymic) factor on the * Supported by the ¢'Sonderforschungsboreich 138" of the Deutsche ForschungsgemeinschaR.

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Section: Assay For Igg Of B Allotypementioning

confidence: 94%

“…Antisera, Anti-sheep red blood cell (SRBC) antiserum of allotype b, and anti-allotype b antiserum reacting with IgG2a b, were used as described (4).…”

mentioning

confidence: 99%

Induction of IgG in young nude mice by lipid A or thymus grafts.

Kolb¹,

Pauli²,

Weiler³

1976

The Journal of Experimental Medicine

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“…The second signal might have been some product of antigen-activated thymus-derived cells (T cells) in the case of T-cell dependent antigens (9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22) or, as postulated for T-cell independent antigens, the second signal could have been associated with the antigen itself (8,(23)(24)(25). With respect to lipopolysaccharide (LPS), 1 a T-cell independent antigen (26)(27)(28), the second signal was reported to reside in the Lipid A portion of the LPS molecule (8,(29)(30)(31)(32).…”

Section: (From the Department Of Microbiology University O[ Montanamentioning

confidence: 99%

“…The second signal might have been some product of antigen-activated thymus-derived cells (T cells) in the case of T-cell dependent antigens (9-22) or, as postulated for T-cell independent antigens, the second signal could have been associated with the antigen itself (8,(23)(24)(25). With respect to lipopolysaccharide (LPS), 1 a T-cell independent antigen (26-28), the second signal was reported to reside in the Lipid A portion of the LPS molecule (8,(29)(30)(31)(32). W o r k in our l a b o r a t o r y has b e e n d i r e c t e d t o w a r d i n v e s t i g a t i n g the i m m u n o l o g i c a l r e s p o n s e s of m i c e i n j e c t e d w i t h L P S (33, 34) or a r e l a t e d m a t e r i a l , n a t i v e p r o t o p l a s m i c p o l y s a c c h a r i d e ( N P P ) (35).…”

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confidence: 99%

Immunological Responses of Mice to Native Protoplasmic Polysaccharide and Lipopolysaccharide

Eschen

Rudbach

1974

The Journal of Experimental Medicine

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There have been several recent hypotheses about the nature of the signals which cause activation of bursa-equivalent cells (B cells) during an immunological response (cf. 1). In one theory it was proposed that a single, antigen-specific signal induced B cells to produce antibodies (2). On the other hand, Coutinho et al. (3) suggested that activation of B cells was the result of one nonspecific signal which was mitogenic for B cells. In a third theory it was postulated that two signals were required to activate B cells to produce antibodies (4-8). These two signals were thought to be (a) the antigenic signal, or the binding of a specific immunodeterminant group to immunoglobulin-like receptors on the surface of a B cell and (b) a second, nonspecific signal. The second signal might have been some product of antigen-activated thymus-derived cells (T cells) in the case of T-cell dependent antigens (9-22) or, as postulated for T-cell independent antigens, the second signal could have been associated with the antigen itself (8,(23)(24)(25). With respect to lipopolysaccharide (LPS), 1 a T-cell independent antigen (26-28), the second signal was reported to reside in the Lipid A portion of the LPS molecule (8,(29)(30)(31)(32). W o r k in our l a b o r a t o r y has b e e n d i r e c t e d t o w a r d i n v e s t i g a t i n g the i m m u n o l o g i c a l r e s p o n s e s of m i c e i n j e c t e d w i t h L P S (33, 34) or a r e l a t e d m a t e r i a l , n a t i v e p r o t o p l a s m i c p o l y s a c c h a r i d e ( N P P ) (35). N P P , e x t r a c t e d from the p r o t o p l a s m of E s c h e r i c h i a coli (36, 37), was a s i m p l e p o l y s a c c h a r i d e w i t h an a v e r a g e mQ1 wt of 163,000 d a l t o n s (38). O n c e t h o u g h t to be a p r o t o p l a s m i c p r e c u r s o r to cell wall*This investigation was supported in part by U. S. Public Health Service Training Grant 5-T01-AI00385. A preliminary report of this work was presented, in part, at the Annual Meeting of the American Society for Microbiology, Chicago, Ill., May 17, 1974. ~Abbreviations used in this paper: LPS, lipopolysaccharide; NPP, native protoplasmic polysaccharide; RML mice, outbred mice from the Rocky Mountain Laboratory stock; nude mice, congenitally athymic nude mice; LPS-0113, LPS from E. coli 0113; LPS-0111, LPS from E. coil 0111; NPP-0113, NPP from E. coli 0113; ReGL-G30/C21, glycolipid from the Re mutant G30/C21 of S. typhimurium; PBS, phosphate-buffered saline; PFC, direct plaque-forming cells; HGG, human gamma globulin.

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“…It was found that the frequency of precursors capable of giving rise to lgM secreting clones was one in six spleen cells, whereas it was one in 60 spleen cells for IgG secreting clones [8,10]. LPS can also trigger in vivo increased formation of IgG since it has been observed that the injection of the lipid A portion of lipopolysaccharides induced increased production of IgG in newborn mice [45].…”

Section: A Activation Of B Lymphocytesmentioning

confidence: 99%