Reticulocyte Maturation and Variant Red Blood Cells.

Christian J Stevens-Hernandez,Sabine Kupzig,Lesley J Bruce,Joanna F Flatt

doi:10.3389/fphys.2022.834463

Christian J Stevens-Hernandez, Sabine Kupzig + Show 2 more

Open Access

https://doi.org/10.3389/fphys.2022.834463

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Abstract

The bone marrow produces billions of reticulocytes daily. These reticulocytes mature into red blood cells by reducing their plasma membrane by 20% and ejecting or degrading residual internal organelles, membranes and proteins not required by the mature cell. This process occurs by autophagy, protein degradation and vesiculation but is not well understood. We previously reported that Southeast Asian Ovalocytic RBCs demonstrate incomplete reticulocyte maturation and we have now extended this study to a number of other variant RBCs. By comparing the profile of a pure reticulocyte preparation of cultured red cells with these variant cells, we show that the largest of these cells, the overhydrated hereditary stomatocytosis cells, are the least mature, they barely reduced their plasma membrane and contain large amounts of proteins that should have been reduced or removed. Intermediate sized variant RBCs appear to be more mature but retain some endoplasmic reticulum and residual membrane proteins. We propose that the size and composition of these variant cell types correlate with the different stages of reticulocyte maturation and provide insight into the reticulocyte maturation process.

Highlights

Introduction200 billion reticulocytes are produced every day in the bone marrow of healthy individuals
On average, 200 billion reticulocytes are produced every day in the bone marrow of healthy individuals
Pure Cultured RBCs (cRBCs) are a mixture of R1 (Figure 1iii) and R2 (Figure 1iv) reticulocytes plus a small number of more mature cells (Figure 1v) resembling fully mature erythrocytes (Figure 1vi)

Summary

Introduction

200 billion reticulocytes are produced every day in the bone marrow of healthy individuals These immature red blood cells (RBCs) must go through a process of maturation to form mature RBCs. Immediately post-enucleation reticulocytes are large (120-140fL) and multilobular. R1 reticulocytes contain residual mitochondria, ribosomes, endoplasmic reticulum (ER) and other internal membranes that are not required by the mature RBC They have excess plasma membrane, which must be reduced by 20%, plus numerous superfluous proteins, e.g., the transferrin receptor (TfR) and various integrins, to be removed from the mature RBC (Koury et al, 1989; Wickrema et al, 1994; Liu et al, 2010). This initial stage of maturation occurs by membrane rearrangement via autophagic, proteolytic, and vesicle-based mechanisms (Minetti et al, 2020) and results in the R2 reticulocytes that are released into the circulation where they mature further

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