A unique role of the cholera toxin A1-DD adjuvant for long-term plasma and memory B cell development
(2011) In Journal of Immunology 186(3). p.1399-1410- Abstract
Adjuvants have traditionally been appreciated for their immunoenhancing effects, whereas their impact on immunological memory has largely been neglected. In this paper, we have compared three mechanistically distinct adjuvants: aluminum salts (Alum), Ribi (monophosphoryl lipid A), and the cholera toxin A1 fusion protein CTA1-DD. Their influence on long-term memory development was dramatically different. Whereas a single immunization i.p. with 4-hydroxy-3-nitrophenyl acetyl (NP)-chicken γ-globulin and adjuvant stimulated serum anti-NP IgG titers that were comparable at 5 wk, CTA1-DD-adjuvanted responses were maintained for >16 mo with a half-life of anti-NP IgG ∼36 wk, but <15 wk after Ribi or Alum. A CTA1-DD dose-dependent... (More)
Adjuvants have traditionally been appreciated for their immunoenhancing effects, whereas their impact on immunological memory has largely been neglected. In this paper, we have compared three mechanistically distinct adjuvants: aluminum salts (Alum), Ribi (monophosphoryl lipid A), and the cholera toxin A1 fusion protein CTA1-DD. Their influence on long-term memory development was dramatically different. Whereas a single immunization i.p. with 4-hydroxy-3-nitrophenyl acetyl (NP)-chicken γ-globulin and adjuvant stimulated serum anti-NP IgG titers that were comparable at 5 wk, CTA1-DD-adjuvanted responses were maintained for >16 mo with a half-life of anti-NP IgG ∼36 wk, but <15 wk after Ribi or Alum. A CTA1-DD dose-dependent increase in germinal center (GC) size and numbers was found, with >60% of splenic B cell follicles hosting GC at an optimal CTA1-DD dose. Roughly 7% of these GC were NP specific. This GC-promoting effect correlated well with the persistence of long-term plasma cells in the bone marrow and memory B cells in the spleen. CTA1-DD also facilitated increased somatic hypermutation and affinity maturation of NP-specific IgG Abs in a dose-dependent fashion, hence arguing that large GC not only promotes higher Ab titers but also high-quality Ab production. Adoptive transfer of splenic CD80+, but not CD80-, B cells, at 1 y after immunization demonstrated functional long-term anti-NP IgG and IgM memory cells. To our knowledge, this is the first report to specifically compare and document that adjuvants can differ considerably in their support of long-term immune responses. Differential effects on the GC reaction appear to be the basis for these differences.
(Less)
- author
- Bemark, Mats LU ; Bergqvist, Peter ; Stensson, Anneli ; Holmberg, Anna ; Mattsson, Johan and Lycke, Nils Y.
- publishing date
- 2011-02-01
- type
- Contribution to journal
- publication status
- published
- in
- Journal of Immunology
- volume
- 186
- issue
- 3
- pages
- 1399 - 1410
- publisher
- American Association of Immunologists
- external identifiers
-
- pmid:21199899
- scopus:79251591958
- ISSN
- 0022-1767
- DOI
- 10.4049/jimmunol.1002881
- language
- English
- LU publication?
- no
- id
- 1f14e200-8548-4225-ac9e-b021b896ad3d
- date added to LUP
- 2023-12-06 16:41:06
- date last changed
- 2024-01-04 15:04:57
@article{1f14e200-8548-4225-ac9e-b021b896ad3d, abstract = {{<p>Adjuvants have traditionally been appreciated for their immunoenhancing effects, whereas their impact on immunological memory has largely been neglected. In this paper, we have compared three mechanistically distinct adjuvants: aluminum salts (Alum), Ribi (monophosphoryl lipid A), and the cholera toxin A1 fusion protein CTA1-DD. Their influence on long-term memory development was dramatically different. Whereas a single immunization i.p. with 4-hydroxy-3-nitrophenyl acetyl (NP)-chicken γ-globulin and adjuvant stimulated serum anti-NP IgG titers that were comparable at 5 wk, CTA1-DD-adjuvanted responses were maintained for >16 mo with a half-life of anti-NP IgG ∼36 wk, but <15 wk after Ribi or Alum. A CTA1-DD dose-dependent increase in germinal center (GC) size and numbers was found, with >60% of splenic B cell follicles hosting GC at an optimal CTA1-DD dose. Roughly 7% of these GC were NP specific. This GC-promoting effect correlated well with the persistence of long-term plasma cells in the bone marrow and memory B cells in the spleen. CTA1-DD also facilitated increased somatic hypermutation and affinity maturation of NP-specific IgG Abs in a dose-dependent fashion, hence arguing that large GC not only promotes higher Ab titers but also high-quality Ab production. Adoptive transfer of splenic CD80<sup>+</sup>, but not CD80<sup>-</sup>, B cells, at 1 y after immunization demonstrated functional long-term anti-NP IgG and IgM memory cells. To our knowledge, this is the first report to specifically compare and document that adjuvants can differ considerably in their support of long-term immune responses. Differential effects on the GC reaction appear to be the basis for these differences.</p>}}, author = {{Bemark, Mats and Bergqvist, Peter and Stensson, Anneli and Holmberg, Anna and Mattsson, Johan and Lycke, Nils Y.}}, issn = {{0022-1767}}, language = {{eng}}, month = {{02}}, number = {{3}}, pages = {{1399--1410}}, publisher = {{American Association of Immunologists}}, series = {{Journal of Immunology}}, title = {{A unique role of the cholera toxin A1-DD adjuvant for long-term plasma and memory B cell development}}, url = {{http://dx.doi.org/10.4049/jimmunol.1002881}}, doi = {{10.4049/jimmunol.1002881}}, volume = {{186}}, year = {{2011}}, }