The immunological properties of haptens coupled to thymus‐independent carrier molecules. I. The characteristics of the immune response to dinitrophenyllysinesubstituted pneumococcal polysaccharide (SIII) and levan

Klaus, G. G. B.; Humphrey, John

doi:10.1002/eji.1830040513

Cited by 64 publications

(26 citation statements)

References 40 publications

(8 reference statements)

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“…This is in agreement with experiments showing lack of enhancement of antibody production in secondary responses to haptenated Ficoll [36]. The longevity of these antibody responses may compensate for the absence of memory.…”

Section: Discussionsupporting

confidence: 90%

T-independent type 2 antigens induce B cell proliferation in multiple splenic sites, but exponential growth is confined to extrafollicular foci

et al. 1999

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During the primary splenic response to the T-independent type 2 (TI-2) antigen (4-hydroxy-3-nitrophenyl) acetyl (NP)-Ficoll, small numbers of antigen-specific B cells have entered S phase of the cell cycle 24 h after intraperitoneal immunization. These are distributed in all splenic compartments (T zones, marginal zones, follicles, and red pulp), indicating early proliferation induced by NP-Ficoll does not require accessory signals delivered in a particular splenic microenvironment. Subsequently B blasts accumulate selectively in the outer T zone areas, but exponential growth leading to plasma cell production occurs only in extra-follicular foci. This growth peaks after 5 days, but 20 % of peak numbers of antibody-containing cells are still present 3 months after immunization and 9 % of these cells are proliferating. It is unclear if these late plasmablasts are sustained by self-renewal or continued recruitment of virgin cells into the response. Unlike TD and TI-1 responses NP-specific memory cells do not accumulate in the splenic marginal zones. The level of C + 3 switch transcripts increases during the first 24 h of the response, but does not increase further during exponential plasmablast growth. Abbreviations: BrdU: 5-Bromo-2'-deoxyuridine TD: Thy-mus dependent TI-2: Thymus independent type-2

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Section: Discussionsupporting

confidence: 90%

T-independent type 2 antigens induce B cell proliferation in multiple splenic sites, but exponential growth is confined to extrafollicular foci

et al. 1999

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“…A highly effective method of inducing hapten-specific (B cell) tolerance is t o administer the hapten on a polymeric, persistent carrier such as type 3 pneumococcal polysaccharide (S3) [ 31. Previous experiments from this laboratory have shown that small doses of haptencoupled S3 (DNP-lys-S3) totally suppress adoptive secondary anti-DNP IgG responses [3]. Subsequently, we found that similar doses induce primary anti-DNP IgM antibody responses in normal mice [4]. The results of dose-response experiments in the latter study suggested that supraoptimal doses of both DNP-lys-S3 and DNP-lys-levan (Le) induced tolerance in unprimed B cells.…”

Section: Introductionmentioning

confidence: 77%

“…Assays for splenic anti-DNP plaque-forming cells (PFC) were performed as previously described [4]. Responses are presented as PFC(spleen, being means f standard errors of groups of 4-5 mice.…”

Section: Antibody-forming Cell Assaysmentioning

confidence: 99%

B cell tolerance induced by polymeric antigens. I. Comparison of thedose and epitope density requirement for inactivation of primed and unprimed B cells in vivo

Klaus

Humphrey

1975

Eur J Immunol

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Hapten [2,4-dinitrophenyl (DNP)]-specific tolerance was induced in nonimmune or DNP-hemocyanin (DNP-KLH) primed mice by administering hapten-conjugated type 3 pneumococcal polysaccharide (DNP-lys-S3). The dose of DNP-lys2.5-S3 required to suppress the primary anti-DNP antibody responses was approximately ten times higher than that required to suppress the secondary response. Large doses of lightly substituted antigen (DNP-lys0.6-S3) had no effect on primary antibody responses, while small doses of this conjugate suppressed 90-95% of the secondary response. The conclusion from this (presumably B cell) tolerance model is that B lymphocytes "mature" in their susceptibility to tolerization following primary contact with immunogen, since primed cells are inactivated by lower doses of tolerogen, and by tolerogen with lower epitope density, than nonimmune B cells. These and other data suggest that the tolerance threshold of B lymphocytes is related to their state of differentiation, and especially to their antigen-binding characteristics.

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“…Thymus-independent antigens induce an immune response in the virtual absence of T lymphocytes and predominantly include polysaccharides (e.g., bacterial capsular polysaccharides and lipopolysaccharides from Gramnegative bacteria) (for example, refs. [28][29][30][31][32][33]. The cellular triggering of B cells is believed to take place without the participation of T cells as a result of the engagement of membrane immunoglobulin by the repeating epitopes of the polysaccharides and/or their intrinsic mitogenic property (as with lipopolysaccharide).…”

Section: Discussionmentioning

confidence: 99%

Effects of pH and polysaccharides on peptide binding to class II major histocompatibility complex molecules.

Harding

Roof

Allen

et al. 1991

Proc. Natl. Acad. Sci. U.S.A.

129

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The binding of immunogenic peptides to class II major histocompatibility molecules was examined at various pH values. We studied binding of peptides containing residues 52-61 from hen egg lysozyme (HEL) to I-Ak on fixed peritoneal macrophages or to solubilized affinity-purified I-Ak. Optimum binding occurred at pH 5.5-6.0 with accelerated kinetics relative to pH 7.4; equilibrium binding was also higher at pH 5.54.0 than at 7. Antigen processing involves the intracellular catabolism of proteins to produce immunogenic peptides that bind to class II major histocompatibility complex (MHC) molecules. A significant proportion of class II MHC molecules resides in endosomes (1-3), where binding of peptides appears to occur (2). Antigen processing involves late endosomes and lysosomes, since it is blocked at 180C (4). Efficient processing occurs with liposome-encapsulated antigens that are sequestered until delivery and release into lysosomes (5). These data suggest that immunogenic peptides produced in lysosomes may be recycled to endosomes to meet and bind to class II MHC molecules. Endosomes maintain an acidic luminal pH (about pH 6 for early endosomes and pH 5-5.5 in later endosomes, whereas lysosomes may attain pH 4.6-5.0). Alkalinization of the endosomal environment (e.g., by lysosomotropic amines or ionophores) disrupts endosomal/lysosomal processes (6), including antigen processing (7). In this context, class II MHC molecules would be expected to bind peptides efficiently at endosomal pH. Previously published data tend to support this hypothesis (8), but the effects of pH on peptide binding remain unclear in many aspects. Peptide dissociation has also been reported to be greater at acidic pH (pH 4.6-5.6) than at neutral pH (9), although other reports indicate that peptides remain stably bound in this pH range (10, 11).We have studied (12-14) the binding of peptides to the murine class II MHC molecule I-Ak on whole cells and as a solubilized afflinity-purified molecule (12-14 Immunogenic peptides were added in unbuffered normal saline and incubated at 37°C for 2 hr (peptides were synthesized and purified as described) (19). The cells were then washed and T-hybridoma cells were added in normal medium. T-cell responses (interleukin 2 secretion) were measured using a CTLL proliferation assay as described (18). We used the following T-cell hybridomas: 3A9, specific for the HEL peptide (21). For peptide dissociation experiments, the peptides were allowed to bind to fixed macrophages in normal medium. The cells were then washed, incubated at various pH values in the above buffers, and washed in regular medium prior to addition of T cells. For studies of the carbohydrates, fixed adherent macrophages or TA3 B-lymphoma cells were incubated with peptides in the presence of the carbohydrates, washed, and then incubated with T-hybridoma cells.

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The immunological properties of haptens coupled to thymus‐independent carrier molecules. I. The characteristics of the immune response to dinitrophenyllysinesubstituted pneumococcal polysaccharide (SIII) and levan

Cited by 64 publications

References 40 publications

T-independent type 2 antigens induce B cell proliferation in multiple splenic sites, but exponential growth is confined to extrafollicular foci

T-independent type 2 antigens induce B cell proliferation in multiple splenic sites, but exponential growth is confined to extrafollicular foci

B cell tolerance induced by polymeric antigens. I. Comparison of thedose and epitope density requirement for inactivation of primed and unprimed B cells in vivo

Effects of pH and polysaccharides on peptide binding to class II major histocompatibility complex molecules.

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