CD16-positive (CD14(++) CD16(+) and CD14(+) CD16(++) ) monocytes have unique features with respect to phenotype and function. We have used transcriptional profiling for comparison of CD16-positive monocytes and classical monocytes. We show herein that 187 genes are greater than fivefold differentially expressed, including 90 genes relevant to immune response and inflammation. Hierarchical clustering of data for monocyte subsets and CD1c(+) myeloid blood dendritic cells (DCs) demonstrate that CD16-positive cells are more closely related to classical monocytes than to DCs. Reverse transcriptase polymerase chain reaction for ten genes with the strongest differential expression confirmed the pattern including a lower messenger RNA level for CD14, CD163, and versican in CD16-positive monocytes. The pattern was similar for CD16-positive monocytes at rest and after exercise mobilization from the marginal pool. By contrast, alveolar macrophages, small sputum macrophages, breast milk macrophages, and synovial macrophages all showed a different pattern. When monocyte-derived macrophages (MDMs) were generated from CD16-positive monocytes by culture with macrophage colony-stimulating factor in vitro, then the MDMs maintained properties of their progeny with lower expression of CD14, CD163, and versican compared with CD14(++) CD16(-) MDMs. Furthermore, CD16-positive MDMs showed a higher phagocytosis for opsonized Escherichia coli. The data demonstrate that CD16-positive monocytes form a distinct type of cell, which gives rise to a distinct macrophage phenotype.
© 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The etiology of chronic lymphocytic leukemia (CLL) is poorly understood and its course is highly variable. Somatic hypermutation (SHM) of the immunoglobulin heavy chain (IgV(H)) gene and ZAP70 protein expression have been reported as prognostic indicators. However, these assays are not widely available and their concordance is imperfect. Thus a need exists to identify additional molecular determinants of CLL. The Igbeta (CD79b) subunit of the B cell antigen receptor is essential for B lymphocyte function. Defects in Igbeta expression are implicated in CLL pathogenesis. We have analyzed Igbeta mRNA expression in CLL cells in 40 consecutive patient samples. About 75% of the samples showed the expected decrease of Igbeta surface staining. Igbeta mRNA levels covered a wider range, did not correlate with Igbeta surface staining, but clearly distinguished the normal and CLL lymphocyte populations. Remarkably, Igbeta mRNA levels correlated strongly with SHM; Igbeta mRNA levels in CLL cells were significantly higher in patients with an unmutated IgV(H) gene when compared with those in whom IgV(H) was hypermutated (P = 0.008). In contrast, no correlation was observed between Igbeta mRNA levels and ZAP70 expression. Multiple parameters abstracted from chart reviews were used to estimate severity of CLL in each case. While severity correlated strongly with ZAP70 staining, and to a lesser extent with SHM status, there was no correlation with Igbeta mRNA levels. These data establish a strong linkage between Igbeta mRNA expression and SHM in CLL and highlight the complex relationships between biochemical parameters and clinical status in this disease.

Random assortment of genes within mammalian genomes establishes the potential for interference between neighboring genes with distinct transcriptional specificities. Long-range transcriptional controls further increase this potential. Exploring this problem is of fundamental importance to understanding gene regulation. In the human genome, the Igbeta (CD79b) gene is situated between the pituitary-specific human growth hormone (hGH) gene and its locus control region (hGH LCR). Igbeta protein is considered B-cell specific; its only known role is in B-cell receptor signaling. Unexpectedly, we found that hIgbeta is transcribed at high levels in the pituitary. This Igbeta transcription is dependent on pituitary-specific epigenetic modifications generated by the hGH LCR. In contrast, expression of Igbeta at its native site in B cells is independent of hGH LCR activity. These studies demonstrated that a gene with tissue-restricted transcriptional determinants (B cell) can be robustly activated in an unrelated tissue (pituitary) due to fortuitous positioning within an active chromatin domain. This 'bystander' gene activation pathway impacts on current concepts of tissue specificity and models of active chromatin domains.