Maturation of humoral immune responses : Studies on the effects of antigen type, apoptosis and age

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.

Occupational titles and supposed gender-neutrality : A corpus-based diachronic study on gender-neutral occupational titles in American English

Traditionally, some occupational titles have been explicitly marked for the gender of the group dominating the occupation. For example, in male-dominated occupations, titles often end with -man. However, since the second-wave feminist movement, several of the previously gender-biased titles have been supplemented by new, gender-neutral titles. Previous research has shown a discrepancy between researchers regarding the implications of these new titles. Some argue that the gender-neutral titles are only used for female referents, whereas others claim that gender-neutral titles, especially for male- dominated occupations, tend to still presuppose maleness. In the present paper, a corpus-based study is conducted on a few selected occupational titles. The aim is to investigate whether the gender-neutral alternatives have increased in usage over time, and whether the gender-biased ones have decreased. In addition, the study aims at examining whether the gender-neutral forms tend to be used primarily for women or men. The present study is corpus-based, examining the particular terms in the TIME Magazine Corpus. The results of the study show that there has been an increase of the gender-neutral forms since their introduction to English, and that they are primarily used when there is no explicit gender referencing. Proposed explanations for these results are that it may depend on the type of work involved in the selected occupations, as well as them being male-dominated. Furthermore, the results indicate that the gender- neutral terms are opted for when gender is either unknown or irrelevant for the context.