B-cell antibody class switchings are pressuromodulated events: Part II, gene recombination

Abstract

Background: The esebssiwaagoT Q method is applicable for the of study cell gene recombination events as the esebssiwaagoT Q is a measure of the intracellular pressure required to establish a horizontal reading frame for alignment of a gene and its intergene bases for maximal transcription and recombination enzyme activity. B-cell differentiation stages have recently been studied by gene esebssiwaagoT Q-based pressuromodulation mapping. In this study, the B-cell differentiation stage pressuromodulation map is utilized as a template to simulate B-cell immunoglobulin locus recombination events that take place in the pressuromodulated state in vivo. Methods: Chromosome 14 (−) strand location 105,566,277 and 106,879,844 germline genes were recombined after determination of gene esebssiwaagoT Q s with respect to the germline, and then recombined genes were recombined further after determination of gene esebssiwaagoT Q s with respect to rearranged configurations. For both alleles, first, IGHD_-_ to IGHJ_ was performed, and then IGHV_-_ to IGHD_-_-IGHJ_ was performed. For Allele 1 (IGHM), internal consensus recognition sequence (iCSR) and further CSR isotype switchings were performed; and for Allele 2 (IGHD), homologous recombination was performed and initial allelic exclusion determined. Results: First, the esebssiwaagoT Q of a joining (J_) and diversity (D_-_) gene in its native germline configuration is the basis for predictable subsequent gene rearrangement. Second, D_-_ to J_ gene recombination events are biallelic and mutually exclusive. Third, the entire process from beginning to end depends on the grade of the pressuromodulation effect, and as per the classical pathway it is an antigen presenting cell (APC)-dependent CD4R+ T-cell-mediated B-cell polarization process. Fourth, CD4R+ T-cells are positively pressuromodulated, while B-cells are subject to the effect of both positive and negative forms of antigen pressuromodulation. And fifth, B-cell to plasma cell transformation and the extra-nodal periphery/tissue nidus phase take place in the presence of antigen load and either positive or negative pressuromodulation of the cell to its recombined antibody gene expression intracellular pressure. Conclusions: B-cell gene recombination rearrangement events can be predicted with a reasonable degree of certainty. It is envisioned that further esebssiwaagoT Q-based study of the remaining B-cell variability gene recombinations isotype switching events will further our understanding of pressuromodulated basis for antigen selection including the evolutionary underpinnings of.

B-cell differentiation is pressuromodulated as determined by pressuromodulation mapping: Part I, cell differentiation

“…For the subset of CD34R+ pluripotent stem cells that divide to mature further in the sub-cortical marrow caverns to express antagonist transcription factor gene PRDM1, it is the overexpression of PRDM1 (esebssiwaa-goT Q : 0.356) and then CD40 and CD40R that drives the cell differentiation process down the B-cell lineage path and starts the V(D)J gene recombination process [20]; whereas, for the subset of CD34R+ stem cells that divide to mature further in the sub-cortical marrow caverns to express transcription factor gene GATA1, it is the overexpression of GATA1 and then the transferrin receptor I gene, TFRC and its endocytic receptor TFR (CD71) that drives the hemopoietic differentiation process down the erythroid lineage path to the anucleated erythrocyte for example [21,22]. The PTPRC, protein product, CD45R, binds to its dendritic cell CM overexpressed receptor ligand on a morphologically sprouted cell type, which polarizes less.…”

“…Therefore, the maximal CD40 expression (CD40R+) period is a function of preceding PRDM1 expression only, while the CD40 non-expression period (CD40R-) is a function of preceeding CD40 and PRDM1 expression in series [20].…”

“…Thus, there is a shift to unimodal expression of the respective BCR subunits as the secretory phase is driven by the antigenic pressuromodulation effect, either positive or negative. The positive antigen pressuromodulator effect via B-plasma cell toll-like receptors (TLR) for example will increase B-cell pressure and maintain it in the supra-pressuromodulated gene expression range (>0.25 esebssiwaagoT Q units) such as in the case of V3-23DJ-IGHM and V1-3DJ-IGHM for example [20]; while, the negative antigen pressuromodulator effect via cell membrane perturbation for example will decrease B-cell pressure and maintain it in the infra-pressuromodulated gene expression range (< 0.25 esebssiwaagoT Q units) such as in the case of V5-51DJ-IGHM [20].…”

“…Thus, an esebssiwaagoT Q match is not necessary in VDJ recombinase-dependent gene recombination [20], as the mechanism is as such.…”

“…APOBEC3H is not a significant contributor as it is expressed at 0.102 units, which is a transient B-cell pressure at the nadir. Thus, post-V(D)J gene internal consensus sequence recognition (iCSR), homologous recombination (HR) and CSR is most efficiently achieved within the 0.281 to 0.158 esebssiwaagoT Q units pressure range, although they do take place at cell pressures as low as 0.13 units [20], for which the APOBEC3C/-D/-F/-G locus expressed enzyme concentrations are sufficient. The upper range for expression is 0.266 plus 0.015 and the lower range is 0.173 minus 0.015 units as the respective genes/gene loci are sufficiently horizontal within ± 0.015 esebssiwaagoT Q units [20].…”