B-cells

B cells, also known as B lymphocytes, are a type of white blood cell of the lymphocyte subtype, that mature in the bone marrow. They express B cell receptors on their surface that allow them to bind specific antigens, and function in the humoral immunity component of the adaptive immune system by secreting antibodies. Additionally, B cells are classical antigen-presenting cells (APCs) and also secrete cytokines.

In the Blood Atlas we have 242 cell lineage enriched genes and 50 of these genes has the highest expression in blood or lymphoid tissues when comparing all tissues and organs analysed. In addition, 464 genes are cell lineage group enriched and an additional 21 genes are enhanced in this cell lineage. Altogether, 727 genes are elevated and among these 152 also show highest expression in blood or lymphoid tissues when comparing all tissues and organs analysed.

Figure 1. The distribution of all genes across the five specificity categories based on transcript abundance in B-cell lineage as well as in the other five cell lineages.

Table 1. Number of genes in the subdivided categories of elevated expression in the B-cell lineage.

Distribution in the six cell lineages
Detected in singleDetected in someDetected in manyDetected in all Total
Specificity
Lineage enriched 1790603 242
Group enriched 0042638 464
Lineage enhanced 21000 21
Total 200048641 727

Table 2. The genes with the highest level of enriched expression in B-cell lineage. "pTPM" shows the transcript level as protein-coding transcripts per million. Specificity-score corresponds to the score calculated as the fold change of B-cell lineage. expression to the second highest cell lineage.*

Gene Description Cell lineage distribution pTPM Specificity score
VPREB3 V-set pre-B cell surrogate light chain 3 Detected in single 837.8 775
AC233755.1 Immunoglobulin heavy variable 4-38-2 Detected in single 497.5 463
IGLL5 immunoglobulin lambda like polypeptide 5 Detected in single 734.2 252
COL19A1 collagen type XIX alpha 1 chain Detected in single 43.1 232
PAX5 paired box 5 Detected in single 48.5 216
AC233755.2 Detected in single 39.7 205
AC141272.1 Detected in single 19.2 155
AC136616.2 Detected in single 24.5 145
WNT16 Wnt family member 16 Detected in single 16.6 132
CTGF connective tissue growth factor Detected in single 10.6 117
CPNE5 copine 5 Detected in single 59.4 111
KLHL14 kelch like family member 14 Detected in single 10.6 108

Naive B-cells

Naive B-cells reside in lymph nodes and are B-cells not yet exposed to an antigen. Upon antigen activation they will differentiate to either plasma cells or memory B-cells.

In the Blood Atlas we have 48 naive B-cell enriched genes and 4 of these genes has the highest expression in blood or lymphoid tissues when comparing all tissues and organs analysed. In addition, 278 genes are cell type group enriched and an additional 193 genes are enhanced in this cell type. Altogether, 519 genes are elevated and among these 118 also show highest expression in blood or lymphoid tissues when comparing all tissues and organs analysed.

The naive B-cells were isolated from PBMCs. Debris and cell aggregates were eliminated based on scatter profiles. Subsequently, monocytes, were eliminated by selecting CD14neg/SSClow sub-population of lymphocytes (FSClow/SSClow). B-cells population was selected as CD19+/CD3neg population. At the final step, population of CD19+/CD27neg naïve B-cells was sorted and 20,000 – 50,000 cells were sorted per sample for transcriptomic analysis by mRNA-sequencing. The transcriptome analysis shows that 54% (n=10695) of all human proteins (n=19,670) are expressed in the naive B-cells and 278 of these genes show an elevated expression in naive B-cells compared to the other 17 cell types (see figure below).

Figure 2. The distribution of all genes across the five specificity categories based on transcript abundance in naive B-cells-cells as well as in the other 17 cell types.

Table 3. Number of genes in the subdivided categories of elevated expression in naive B-cells.

Distribution in the 18 cell types
Detected in singleDetected in someDetected in manyDetected in all Total
Specificity
Cell type enriched 38820 48
Group enriched 0183896 278
Cell type enhanced 4884583 193
Total 862751499 519

Table 4. The genes with the highest level of enriched expression in naive B-cells. "pTPM" shows the transcript level as protein-coding transcripts per million. Specificity-score corresponds to the score calculated as the fold change of naive B-cell expression to the second highest cell type.

Gene Description Cell type distribution pTPM Specificity score
FMO1 flavin containing monooxygenase 1 Detected in single 0.9 36
SYN3 synapsin III Detected in single 4.0 29
KCNG1 potassium voltage-gated channel modifier subfamily G member 1 Detected in single 9.0 27
CRMP1 collapsin response mediator protein 1 Detected in single 0.5 25
CXorf65 chromosome X open reading frame 65 Detected in single 0.4 23
SPATA18 spermatogenesis associated 18 Detected in single 0.4 23
FOXD4L1 forkhead box D4 like 1 Detected in single 0.4 22
DAZL deleted in azoospermia like Detected in single 0.5 21
GRB7 growth factor receptor bound protein 7 Detected in single 0.3 20
DSP desmoplakin Detected in single 2.6 19
PRSS45 serine protease 45 Detected in single 0.2 19
PTH2 parathyroid hormone 2 Detected in single 0.5 18

Memory B-cells

Memory B-cells are formed within germinal centers following primary infection, and are important in generating an accelerated and more robust antibody-mediated immune response in the case of re-infection. They are localized in areas of facilitated antigen encounter and compared to naive B-cells they have higher affinity to the immunizing antigen, a lifespan of decades instead of weeks, and faster and more efficient proliferation and differentiation.

In the Blood Atlas we have 45 memory B-cell enriched genes and 4 of these genes has the highest expression in blood or lymphoid tissues when comparing all tissues and organs analysed. In addition, 284 genes are cell type group enriched and an additional 189 genes are enhanced in this cell type. Altogether, 518 genes are elevated and among these 121 also show highest expression in blood or lymphoid tissues when comparing all tissues and organs analysed.

The memory B-cells were isolated from PBMCs. Debris and cell aggregates were eliminated based on scatter profiles. Subsequently, monocytes were eliminated by selecting CD14neg/SSClow sub-population of lymphocytes (FSClow/SSClow). B-cells population was selected as CD19+/CD3neg population. At the final step, population of CD19+/CD27+ memory B-cells was sorted and 5,000 – 19,000 cells were sorted per sample for transcriptomic analysis by mRNA-sequencing. The transcriptome analysis shows that 53% (n=10370) of all human proteins (n=19,670) are expressed in the memory B-cells and 284 of these genes show an elevated expression in memory B-cells compared to the other 17 cell types (see figure below).

Figure 3. The distribution of all genes across the five specificity categories based on transcript abundance in memory B-cells as well as in the other 17 cell types.

Table 5. Number of genes in the subdivided categories of elevated expression in memory B-cells.

Distribution in the 18 cell types
Detected in singleDetected in someDetected in manyDetected in all Total
Specificity
Cell type enriched 41400 45
Group enriched 0185936 284
Cell type enhanced 4494501 189
Total 852831437 518

Table 6. The genes with the highest level of enriched expression in memory B-cells. "pTPM" shows the transcript level as protein-coding transcripts per million. Specificity-score corresponds to the score calculated as the fold change of memory B-cells expression to the second highest cell type.

Gene Description Cell type distribution pTPM Specificity score
TAS1R3 taste 1 receptor member 3 Detected in single 2.0 37
AMPD1 adenosine monophosphate deaminase 1 Detected in single 0.6 31
FA2H fatty acid 2-hydroxylase Detected in single 0.6 24
PPP1R37 protein phosphatase 1 regulatory subunit 37 Detected in single 0.3 23
TUBB2B tubulin beta 2B class IIb Detected in single 0.3 21
SAA4 serum amyloid A4, constitutive Detected in single 0.2 20
PROX1 prospero homeobox 1 Detected in single 0.2 20
OR4C6 olfactory receptor family 4 subfamily C member 6 Detected in single 0.2 18
SDC1 syndecan 1 Detected in single 1.2 17
EYA2 EYA transcriptional coactivator and phosphatase 2 Detected in single 0.4 16
ARL14 ADP ribosylation factor like GTPase 14 Detected in single 2.0 15
TMEM74 transmembrane protein 74 Detected in single 0.1 14