Abstract
The B cell population is highly diverse and very skewed. It is divided into clones (B cells with a common mother cell). It is thought that each clone represents an initial B cell receptor specificity. A few clones are very abundant, comprised of hundreds or thousands of B cells while the majority have only a few cells per clone. We suggest a novel method - domain-based latent personal analysis (LPA), a method for spectral exploration of entities in a domain, which can be used to find the spectral spread of sub repertoires within a person. LPA defines a domain-based spectral signature for each sub repertoire. LPA signatures consist of the elements, in our case - the clones, that most differentiate the sub repertoire from the person’s abundance of clones. They include both positive elements, which describe overabundant clones, and negative elements that describe missing clones. The signatures can also be used to compare the sub repertoires they represent to each other. Applying LPA to compare the repertoires found in different tissues, we reiterated previous findings that showed that gut and blood tissues have separate repertoires. We further identify a third branch of clonal patterns typical of the lymphatic organs (Spleen, MLN, and bone marrow) separated from the other two categories. We developed a python version of LPA analysis that can easily be applied to compare clonal distributions - https://github.com/ScanLab-ossi/LPA. It could also be easily adapted to study other skewed sequence populations used in the analysis of B cell receptor populations, for instance, k-mers and V gene usage. These analysis types should allow for inter and intra-repertoire comparisons of diversity, which could revolutionize the way we understand repertoire changes and diversity.
Highlights
The extremely high diversity of B cell and T cell receptors in the immune repertoire is key for immune function and protection from disease [1]
We show how applying latent personal analysis (LPA) to the B cell populations of six individuals scanned across eight different tissues allows us to observe both known relationships between repertoires found in gut and blood tissues [21] and new relationships between the different lymphoid tissues, as observed by the differences in clonal distribution and clonal dominance
The tissues are clearly delineated, we find less clear patterns (Supplemental Materials File 5 - by tissue distance heatmaps and networks). This is not surprising given that none of the other individuals were sufficiently sampled to describe even the expanded clone diversity in their B cell receptor populations [21] and only d181, which is relatively well sampled, showed a progression of its signature threshold that was similar to that in D207 (Supplemental Materials File 3 - Signature cutoff interactive Figures)
Summary
The extremely high diversity of B cell and T cell receptors in the immune repertoire is key for immune function and protection from disease [1]. The long-tail distribution results from the auto-catalytic nature of the systems underlying these distributions, where abundance and proliferation are linked to use and functionality [17, 18]. In the T cell repertoire, it has been shown that the long-tail distribution of T cell receptors makes it likely for an antigen to be presented to rare or common T cell receptor types [1] In this way, the T cell distribution allows both rare and common T cells to be tested for their affinity when the immune system is activated and searching for a receptor response to disease
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