Walter and Eliza Hall Institute of Medical Research

About: Walter and Eliza Hall Institute of Medical Research is a nonprofit organization based out in Melbourne, Victoria, Australia. It is known for research contribution in the topics: Antigen & Immune system. The organization has 5012 authors who have published 10620 publications receiving 873561 citations.

The rising incidence of type 1 diabetes is accounted for by cases with lower-risk human leukocyte antigen genotypes.

Abstract: Objective: The rising incidence of type 1 diabetes has been attributed to environment, implying a lesser role for genetic susceptibility. However, the rise could be accounted for either by more cases with classic high risk genes or by cases with other risk genes. Separately, for any degree of genetic susceptibility, age at presentation may decrease in a permissive environment. To examine these possibilities, HLA class II DRB1 genes known to confer risk for type 1 diabetes were analysed in relation to year of birth and age at diagnosis over the last five decades. Research Design and Methods: Caucasoid subjects (n=462) diagnosed with type 1 diabetes before age 18 between 1950 and 2005 were DRB1 genotyped. Results: Mean age at diagnosis, 8.5 years (SD 4.5 years), did not differ across decades. Recent diagnosis was associated with a lower proportion but unchanged incidence of the highest risk DRB1 genotype DR3,4 (2000-05: 28% vs 1950-1969: 79%; p Conclusions: The rising incidence and decreasing age at diagnosis of type 1 diabetes is accounted for by the impact of environment on children with lower risk HLA class II genes, who previously would not have developed type 1 diabetes in childhood.

Evidence from the generation of immunoglobulin G–secreting cells that stochastic mechanisms regulate lymphocyte differentiation

Abstract: Naive B lymphocytes undergo isotype switching and develop into immunoglobulin-secreting cells to generate the appropriate class and amount of antibody necessary for effective immunity. Although this seems complex, we report here that the generation of immunoglobulin G–secreting cells from naive precursors is highly predictable. The probabilities of isotype switching and development into secreting cells change with successive cell divisions and interleave independently. Cytokines alter the probability of each differentiation event, while leaving intact their independent assortment. As a result, cellular heterogeneity arises automatically as the cells divide. Stochastic division-linked regulation of heterogeneity challenges the conventional paradigms linking distinct phenotypes to unique combinations of signals and has the potential to simplify our concept of immune complexity considerably.

Activation-induced B cell fates are selected by intracellular stochastic competition.

Abstract: In response to stimulation, B lymphocytes pursue a large number of distinct fates important for immune regulation. Whether each cell’s fate is determined by external direction, internal stochastic processes, or directed asymmetric division is unknown. Measurement of times to isotype switch, to develop into a plasmablast, and to divide or to die for thousands of cells indicated that each fate is pursued autonomously and stochastically. As a consequence of competition between these processes, censorship of alternative outcomes predicts intricate correlations that are observed in the data. Stochastic competition can explain how the allocation of a proportion of B cells to each cell fate is achieved. The B cell may exemplify how other complex cell differentiation systems are controlled.