Fig. 4

The RNA-Seq identified five down-regulated genes encoding proteins associated with B cell differentiation and survival. FLT3 encodes FLT3 (fms-related tyrosine kinase 3), which is important during the very early stages of differentiation in the bone marrow of the hematopoietic stem cell into the Pro-B cell. EBF1 encodes EBF (early B-cell factor 1), which is important during all stages of B cell differentiation except for the plasma cell. CD79A encodes Igα (immunoglobulin-associated alpha), which is a co-molecule in the membrane bound Pre-BCR and the BCR, and ensures a functional receptor. TNFRSF13C encodes BAFFR (B-cell activating factor receptor), which is important for the peripheral B cells to receive survival signal. CXCR5 encodes CXCR5 [chemokine (C-X-C motif) receptor 5], which ensures that matured B cells migrate to B cell follicles of the spleen and Peyer patches. Assuming that the down-regulation of these genes is reflected at the protein and pathway level, our data suggest that the efficiency of B cell differentiation is impaired and that their survival is reduced in the CFS. HSC hematopoietic stem cell, BCR B cell receptor, B B cell, Ig immunoglobulin