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The role of Blimp-1 in the GC reaction: Differential expression of Blimp-1 upon immunization with TD and TI antigens
Stockholm University, Faculty of Science, The Wenner-Gren Institute .
2007 (English)In: Immunology Letters, ISSN 0165-2478, Vol. 113, no 2, 70-75 p.Article in journal (Refereed) Published
Abstract [en]

Humoral responses against thymus-dependent (TD) antigens are characterized by Ig class switch, somatic hypermutations (SHM) and generation of memory. These processes are thought to occur in the specialized environment of the germinal center (GC). Some thymus-independent (TI) antigens, such as native dextran B512 (Dx) can also induce formation of GCs, but the responses do not undergo substantial affinity maturation or induction of memory. Immunization with TI Dx affects later TD responses against the same epitope, reducing Dx specific IgG 1. We have studied if the different outcome of the TI- and TD-induced GC reaction is due to differences in plasma cell differentiation. The transcriptional repressor B lymphocyte-induced maturation protein, Blimp- 1, was used as a marker for differentiation of plasma cells. We show that TI GCs contain Blimp- I in early and mature GCs, in contrast to TD-induced GCs which strongly express Blimp- I only in established GCs. Furthermore, the intensity of the Blimp- I staining is stronger in TI GCs. In addition, we demonstrate that in TD responses after TI priming the pattern of Blimp- I expression is a mixture of both TI and TD responses. This is novel evidence since these TD Immoral responses against Dx display a TI isotype pattern.

Place, publisher, year, edition, pages
2007. Vol. 113, no 2, 70-75 p.
URN: urn:nbn:se:su:diva-25719DOI: 10.1016/j.imlet.2007.07.018ISI: 000250852500002OAI: diva2:200367
Part of urn:nbn:se:su:diva-85Available from: 2004-03-31 Created: 2004-03-31 Last updated: 2010-01-18Bibliographically approved
In thesis
1. Maturation of humoral immune responses: Studies on the effects of antigen type, apoptosis and age
Open this publication in new window or tab >>Maturation of humoral immune responses: Studies on the effects of antigen type, apoptosis and age
2004 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The humoral immune response is dependent on the formation of antibodies. Antibodies are produced by terminally differentiated B cells, plasma cells. Plasma cells are generated either directly from antigen challenged B cells, memory cells or from cells that have undergone the germinal center (GC) reaction. The GC is the main site for class switch, somatic hypermutation and generation of memory cells.

Different factors, both internal and external, shape the outcome of the immune response. In this thesis, we have studied a few factors that influence the maturation of the humoral response. We have studied how age affects the response, and we show that responses against thymus dependent antigens (TD) are more affected than responses to thymus independent (TI) antigens, in concordance with the view that the T cell compartment is more affected by age than the B cell compartment. Furthermore, we demonstrate that priming early in life have a big influence on the immune response in the aged individual. Priming with a TI form of the carbohydrate dextran B512 (Dx) induces a reduction of IgG levels in later TD responses against Dx. We have evaluated possible mechanisms for this reduction. The reduction does not seem to be caused by clonal exhaustion or antibody mediated mechanisms. We also showed that the reduced TD response after TI priming can be induced against another molecule than Dx. With the hypothesis that TI antigens induce a plasma cell biased maturation of the responding B cells, we examined the presence of Blimp-1, a master regulator of plasma cell differentiation, in GCs induced by TD and TI antigen. Blimp-1 was found earlier in GCs induced by TI antigen and the staining intensity in these GCs was stronger than in TD antigen induced GCs, indicating that plasma cells might be continuously recruited from these GCs.

B cells undergoing the GC reaction are thought to be under a strict selection pressure that removes cells with low affinity for the antigen and also cells that have acquired self-reactivity. We investigated the effect of apoptotic deficiencies on the accumulation of somatic mutations in GC B cells. In mice lacking the death receptor Fas, lpr mice, the frequency of mutations was increased but the pattern of the mutations did not differ from wild type mice. In contrast, mice over-expressing the anti-apoptotic protein Bcl-2, had a lowered frequency of mutations and the mutations introduced had other characteristics.

Place, publisher, year, edition, pages
Stockholm: Wenner-Grens institut för experimentell biologi, 2004. 60 p.
immunology, B cell, humoral immune response
National Category
Immunology in the medical area
urn:nbn:se:su:diva-85 (URN)91-7265-835-5 (ISBN)
Public defence
2004-04-21, Nordenskiöldsalen, Geovetenskapens hus, Svante Arrhenius väg 8 C, Stockholm, 10:00
Available from: 2004-03-31 Created: 2004-03-31Bibliographically approved

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