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The B cell receptor itself can activate complement to provide the complement receptor 1/2 ligand required to enhance B cell immune responses in vivo.

Rossbacher J, Shlomchik MJ - J. Exp. Med. (2003)

Bottom Line: B cells express complement receptors (CRs) that bind activated fragments of C3 and C4.CR ligands were thought to be generated via complement fixation mediated by preexisting "natural" IgM or early Ab from inefficiently activated B cells.These results demonstrate a new BCR-dependent pathway that is sufficient and perhaps necessary to provide a CR1/2 ligand that promotes efficient B cell activation.

View Article: PubMed Central - PubMed

Affiliation: Serction of Immunobiology and Department of Laboratory Medicine, Yale University School of Medicine, New Haven, CT 06520-8035, USA.

ABSTRACT
B cells express complement receptors (CRs) that bind activated fragments of C3 and C4. Immunized CR knockout (KO) mice have lower antibody titers and smaller germinal centers (GCs), demonstrating the importance of CR signals for the humoral immune response. CR ligands were thought to be generated via complement fixation mediated by preexisting "natural" IgM or early Ab from inefficiently activated B cells. This concept was recently challenged by a transgenic (Tg) mouse model that lacks circulating antibody but still retains membrane IgM (mIgM) and mounts normal immune responses. To test whether CR ligands could be generated by the B cell receptor (BCR) itself, we generated similar mice carrying a mutated mIgM that was defective in C1q binding. We found that B cells from such mutant mice do not deposit C3 on B cells upon BCR ligation, in contrast to B cells from mIgM mice. This has implications for the immune response: the mutant mice have smaller GCs than mIgM mice, and they are particularly deficient in the maintenance of the GC response. These results demonstrate a new BCR-dependent pathway that is sufficient and perhaps necessary to provide a CR1/2 ligand that promotes efficient B cell activation.

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FACS® analysis of immune responses. Red cell–depleted splenocytes were stained as indicated and 105 events were collected per sample on a FACSCalibur™. Antigen-specific B cell expansion was measured by gating on λ+/NIP+, live splenocytes. Representative data of day 12 after immunization with NP22-CGG are shown here and summarized in Fig. 3 and Table I.
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fig2: FACS® analysis of immune responses. Red cell–depleted splenocytes were stained as indicated and 105 events were collected per sample on a FACSCalibur™. Antigen-specific B cell expansion was measured by gating on λ+/NIP+, live splenocytes. Representative data of day 12 after immunization with NP22-CGG are shown here and summarized in Fig. 3 and Table I.

Mentions: Primary immune responses were initially evaluated at day 12, the known peak of the response in mIgM mice (33). To evaluate a range of different “strengths” of stimulation, two different carriers were chosen and haptenated at two different ratios. Each carrier and haptenation ratio was used for immunization at two different doses, 50 μg as used in all previous immunizations of mIgM mice, and 5 μg as a low Ag dose, for a total of 6 conditions. The B cell immune response was measured via the expansion of λ+/NIP+ cells as determined by FACS® analysis (Fig. 2) . As will be detailed below, in all experiments performed we observed that the immune response of mIgM(P436S) mice was significantly lower than in mIgM mice with especially noticeable differences from the mIgM mice at the low dose of Ag (Table I). Nevertheless, the mIgM(P436S) mice responded to all immunization regimes.


The B cell receptor itself can activate complement to provide the complement receptor 1/2 ligand required to enhance B cell immune responses in vivo.

Rossbacher J, Shlomchik MJ - J. Exp. Med. (2003)

FACS® analysis of immune responses. Red cell–depleted splenocytes were stained as indicated and 105 events were collected per sample on a FACSCalibur™. Antigen-specific B cell expansion was measured by gating on λ+/NIP+, live splenocytes. Representative data of day 12 after immunization with NP22-CGG are shown here and summarized in Fig. 3 and Table I.
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Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2194168&req=5

fig2: FACS® analysis of immune responses. Red cell–depleted splenocytes were stained as indicated and 105 events were collected per sample on a FACSCalibur™. Antigen-specific B cell expansion was measured by gating on λ+/NIP+, live splenocytes. Representative data of day 12 after immunization with NP22-CGG are shown here and summarized in Fig. 3 and Table I.
Mentions: Primary immune responses were initially evaluated at day 12, the known peak of the response in mIgM mice (33). To evaluate a range of different “strengths” of stimulation, two different carriers were chosen and haptenated at two different ratios. Each carrier and haptenation ratio was used for immunization at two different doses, 50 μg as used in all previous immunizations of mIgM mice, and 5 μg as a low Ag dose, for a total of 6 conditions. The B cell immune response was measured via the expansion of λ+/NIP+ cells as determined by FACS® analysis (Fig. 2) . As will be detailed below, in all experiments performed we observed that the immune response of mIgM(P436S) mice was significantly lower than in mIgM mice with especially noticeable differences from the mIgM mice at the low dose of Ag (Table I). Nevertheless, the mIgM(P436S) mice responded to all immunization regimes.

Bottom Line: B cells express complement receptors (CRs) that bind activated fragments of C3 and C4.CR ligands were thought to be generated via complement fixation mediated by preexisting "natural" IgM or early Ab from inefficiently activated B cells.These results demonstrate a new BCR-dependent pathway that is sufficient and perhaps necessary to provide a CR1/2 ligand that promotes efficient B cell activation.

View Article: PubMed Central - PubMed

Affiliation: Serction of Immunobiology and Department of Laboratory Medicine, Yale University School of Medicine, New Haven, CT 06520-8035, USA.

ABSTRACT
B cells express complement receptors (CRs) that bind activated fragments of C3 and C4. Immunized CR knockout (KO) mice have lower antibody titers and smaller germinal centers (GCs), demonstrating the importance of CR signals for the humoral immune response. CR ligands were thought to be generated via complement fixation mediated by preexisting "natural" IgM or early Ab from inefficiently activated B cells. This concept was recently challenged by a transgenic (Tg) mouse model that lacks circulating antibody but still retains membrane IgM (mIgM) and mounts normal immune responses. To test whether CR ligands could be generated by the B cell receptor (BCR) itself, we generated similar mice carrying a mutated mIgM that was defective in C1q binding. We found that B cells from such mutant mice do not deposit C3 on B cells upon BCR ligation, in contrast to B cells from mIgM mice. This has implications for the immune response: the mutant mice have smaller GCs than mIgM mice, and they are particularly deficient in the maintenance of the GC response. These results demonstrate a new BCR-dependent pathway that is sufficient and perhaps necessary to provide a CR1/2 ligand that promotes efficient B cell activation.

Show MeSH
Related in: MedlinePlus