Kindlin-3 maintains marginal zone B cells but confines follicular B cell activation and differentiation

Integrin-mediated interactions between hematopoietic cells and their microenvironment are important for the development and function of immune cells. Here, the role of the integrin adaptor Kindlin-3 in B cell homeostasis is studied. Comparing the individual steps of B cell development in B cell-specific Kindlin-3 or alpha4 integrin knockout mice, we found in both conditions a phenotype of reduced late immature, mature, and recirculating B cells in the bone marrow. In the spleen, constitutive B cell-specific Kindlin-3 knockout caused a loss of marginal zone B cells and an unexpected expansion of follicular B cells. Alpha4 integrin deficiency did not induce this phenotype. In Kindlin-3 knockout B cells VLA-4 as well as LFA-1-mediated adhesion was abrogated, and short-term homing of these cells in vivo was redirected to the spleen. Upon inducible Kindlin-3 knockout, marginal zone B cells were lost due to defective retention within 2 weeks, while follicular B cell numbers were unaltered. Kindlin-3 deficient follicular B cells displayed higher IgD, CD40, CD44, CXCR5, and EBI2 levels, and elevated PI3K signaling upon CXCR5 stimulation. They also showed transcriptional signatures of spontaneous follicular B cell activation. This activation manifested in scattered germinal centers in situ, early plasmablasts differentiation, and signs of IgG class switch

Recovery from black spots: results of a loading experiment in the Wadden Sea

In field experiments to study the response of intertidal flats to the burial of organic carbon, we loaded southern North Sea sandy sediments with varying amounts of starch. The loaded areas temporarily turned black due to sulphate-reducing degradation of the organic burden. The appearance and disappearance of black sediment surfaces were monitored over a period of 12 months by means of pore-water and particulate-matter analysis; organic-matter degradation was traced by delta(13)C (TOC). Biogeochemical data showed the duration and severity of 'black-spot disease' to depend on the amount of organic carbon buried. Results met expectations in a qualitative manner; several causes of the absence of linear correlations between the initial organic-carbon load and DOC or sulphate concentrations are discussed. The critical experimental load that caused black spots ranged between 0.4 and 0.8 kg m(-2) C-org for a single organic-carbon entry. Given a situation of annually repeated entries, we estimate the critical load to be less than 0.4 kg m(-2) a(-1) C-org. Depth profiles indicate OM-caused enrichment in sulphur and pyritisation below 20 cm depth. This study emphasises the conditions of recovery. (C) 1998 Elsevier Science B.V. All rights reserved